Andreas Prokop

• Professor
• Professor at The University of Manchester

Axons are the slender, often meter-long projections of neurons that form the biological cables wiring our bodies. Most of these delicate structures must survive for an organism’s lifetime, meaning up to a century in humans. Long-term maintenance and sustained functionality of axons requires motor protein-driven transport distributing life-sustainin...

Actin is the most abundant protein in eukaryotic cells. They form filamentous polymers that are organized in different ways within the cell to perform various functions. For instance, prominent parallel bundles of F-actins mediate the formation and dynamics of filopodia that are long, finger-like protrusions of cell membrane occurring in certain ce...

Axons are processes of neurons, up to a metre long, that form the essential biological cables wiring nervous systems. They must survive, often far away from their cell bodies and up to a century in humans. This requires self-sufficient cell biology including structural proteins, organelles, and membrane trafficking, metabolic, signalling, translati...

Axons are the narrow, up-to-meter long cellular processes of neurons that form the biological cables wiring our nervous system. Most axons must survive for an organism’s lifetime, i.e. up to a century in humans. Axonal maintenance depends on loose bundles of microtubules that run without interruption all along axons. The continued turn-over and the...

Axons are the long and slender processes of neurons constituting the biological cables that wire the nervous system. The growth and maintenance of axons require loose microtubule bundles that extend through their entire length. Understanding microtubule regulation is therefore an essential aspect of axon biology. Key regulators of neuronal microtub...

For 36 years, the acetylation of lysine 40 in α-tubulin has provided the paradigm for how post-translational acetylation stabilises microtubules. A new study demonstrates that acetylation of lysine 394 in α-tubulin also mediates microtubule stabilisation in neurons.

Axons are the slender, up to meter-long projections of neurons that form the biological cables wiring our bodies. Most of these delicate structures must survive for an organism's lifetime, meaning up to a century in humans. Axon maintenance requires life-sustaining motor protein-driven transport distributing materials and organelles from the distan...

Axons are the long and slender processes of neurons constituting the biological cables that wire the nervous system. The growth and maintenance of axons require bundles of microtubules that extend through their entire length. Understanding microtubule regulation is therefore an essential aspect of axon biology. Key regulators of neuronal microtubul...

The formation and maintenance of microtubules requires their polymerisation, but little is known about how this polymerisation is regulated in cells. Focussing on the essential microtubule bundles in axons of Drosophila and Xenopus neurons, we show that the plus-end scaffold Eb1, the polymerase XMAP215/Msps and the lattice-binder Tau co-operate int...

The number of acquired or inherited conditions leading to axon degeneration (from now on referred to as axonopathies) is vast. To diagnose patients, clinicians use a range of indicators including physiology, morphology, family and patient history, as well as genetics, with the specific location of the lesion within the nervous system being a promin...

Axons are the enormously long cable-like cellular processes of neurons that wire nervous systems and have to survive for up to a century in humans. We lose ~40% of axons towards high age and far more in neurodegenerative diseases. Sustaining axons requires axonal transport and dynamic morphogenetic changes, both crucially dependent on bundles of mi...

Cortical collapse factors affect microtubule (MT) dynamics at the plasma membrane. They play important roles in neurons, as suggested by inhibition of axon growth and regeneration through the Arf activator Efa6 in C. elegans, and by neurodevelopmental disorders linked to the mammalian kinesin Kif21A. How cortical collapse factors influence axon gro...

Abstract Axons are the slender, cable-like, up to meter-long projections of neurons that electrically wire our brains and bodies. In spite of their challenging morphology, they usually need to be maintained for an organism's lifetime. This makes them key lesion sites in pathological processes of ageing, injury and neurodegeneration. The morphology...

Axons are the slender, cable-like, up to meter-long projections of neurons that electrically wire our brain and body. In spite of their challenging morphology, they usually need to be maintained for an organism's lifetime. This makes them key lesion sites in pathological processes of ageing, injury and neurodegeneration. To better understand how ax...

Cortical collapse factors affect microtubule (MT) dynamics at the plasma membrane. They play important roles in neurons, as suggested by inhibition of axon growth and regeneration through the Arf activator Efa6 in C. elegans , and by neurodevelopmental disorders linked to the mammalian kinesin Kif21A. How cortical collapse factors influence axon gr...

Microtubules are filamentous tubular protein polymers which are essential for a range of cellular behaviour, and are generally straight over micron length scales. However, in some gliding assays, where microtubules move over a carpet of molecular motors, individual microtubules can also form tight arcs or rings, even in the absence of crosslinking...

Microtubules are filamentous tubular protein polymers which are essential for a range of cellular behaviour, and are generally straight over micron length scales. However, in some gliding assays, where microtubules move over a carpet of molecular motors, individual microtubules can also form tight arcs or rings, even in the absence of crosslinking...

The aim of this special issue on science communication is to inspire and help scientists who are taking part or want to take part in science communication and engage with the wider public, clinicians, other scientists or policy makers. For this, some articles provide concise and accessible advice to individual scientists, science networks, or learn...

Science communication is becoming an increasingly important part of a scientist's remit, and engaging with primary and secondary schools is one frequently chosen strategy. Here we argue that engaging with schools will be more effective when engaging with teachers through structured participation and/or collaboration, in order to respond to the real...

Spectraplakins are evolutionarily well conserved cytoskeletal linker molecules that are true members of three protein families: plakins, spectrins and Gas2-like proteins. Spectraplakin genes encode at least 7 characteristic functional domains which are combined in a modular fashion into multiple isoforms, and which are responsible for an enormous b...

Science communication is increasingly important for scientists, although research, teaching and administration activities tend to eat up our time already, and budgets for science communication are usually low. It appears impossible to combine all these tasks and, in addition, to develop engagement activities to a quality and impact that would make...

Spectraplakins are evolutionarily well conserved cytoskeletal linker molecules that are true members of three protein families: plakins, spectrins and Gas2-like proteins. Spectraplakin genes encode at least 7 characteristic functional domains which are combined in a modular fashion into multiple isoforms, and which are responsible for an enormous b...

Communicating science to wider lay audiences is an increasingly important part of a scientist's remit, and is something that many scientists are keen to embrace. However, based on surveys carried out amongst the UK public, as well as our own experiences in developing and delivering such activities, we believe that they are not always as effective a...

Axons are the cable-like neuronal processes wiring the nervous system. They contain parallel bundles of microtubules as structural backbones, surrounded by regularly-spaced actin rings termed the periodic membrane skeleton (PMS). Despite being an evolutionarily-conserved, ubiquitous, highly-ordered feature of axons, the function of PMS is unknown....

Axons are the cable-like protrusions of neurons which wire up the nervous system. Polar bundles of microtubules (MTs) constitute their structural backbones and are highways for life-sustaining transport between proximal cell bodies and distal synapses. Any morphogenetic changes of axons during development, plastic rearrangement, regeneration or deg...

Axons are the cable-like protrusions of neurons which wire up the nervous system. Polar bundles of microtubules (MTs) constitute their structural backbones and are highways for life-sustaining transport between proximal cell bodies and distal synapses. Any morphogenetic changes of axons during development, plastic rearrangement, regeneration or deg...

Summary of the statistics from Figure 1B and C.DOI: http://dx.doi.org/10.7554/eLife.14694.004

Summary of the statistics from Figure 1—figure supplement 2B.DOI: http://dx.doi.org/10.7554/eLife.14694.007

Summary of the statistics from Figure 5—figure supplement 1B.DOI: http://dx.doi.org/10.7554/eLife.14694.024

Summary statistics from Figure 8—figure supplement 1B.DOI: http://dx.doi.org/10.7554/eLife.14694.034

Summary of the statistics from Figure 3—figure supplement 1B.DOI: http://dx.doi.org/10.7554/eLife.14694.014

Summary of the statistics from Figure 4B–D.DOI: http://dx.doi.org/10.7554/eLife.14694.020

Summary of the statistics from Figure 6C and E.DOI: http://dx.doi.org/10.7554/eLife.14694.026

Summary of the statistics from Figure 6—figure supplement 1B.DOI: http://dx.doi.org/10.7554/eLife.14694.028

Summary of the statistics from Figure 8B,D and F.DOI: http://dx.doi.org/10.7554/eLife.14694.032

Summary of the statistics from Figure 1—figure supplement 3C and D.DOI: http://dx.doi.org/10.7554/eLife.14694.018

Summary of the statistics from Figure 2B.DOI: http://dx.doi.org/10.7554/eLife.14694.009

Summary of the statistics from Figure 3B,D,F.DOI: http://dx.doi.org/10.7554/eLife.14694.012

Summary of the statistics from Figure 5.DOI: http://dx.doi.org/10.7554/eLife.14694.022

The mechanisms regulating synapse numbers during development and ageing are essential for normal brain function and closely linked to brain disorders including dementias. Using Drosophila, we demonstrate roles of the microtubule-associated protein Tau in regulating synapse numbers, thus unravelling an important cellular requirement of normal Tau. I...

Actin and microtubules are components of the cytoskeleton, and are key mediators of neuron growth and maintenance. Knowing how they are regulated enhances our understanding of neural development, ageing, degeneration and re-generation. However, biological investigation alone will not unravel the complex cytoskeletal machinery. We expect that inquir...

Communicating science to wider lay audiences is of increasing importance and is becoming an ever larger part of a scientist's remit which also offers important opportunities. We discuss here the current state of science communication in the field of the natural sciences in the UK, and the enormous improvements that could be achieved through putting...

The droso4schools project is a novel and creative approach to bringing the fruit fly Drosophila back into school biology lessons. These small insects are powerful, modern teaching tools, ideal for explaining many concepts that underlie curriculum-relevant biology specifications and illustrating the links between them. Flies are cost-effective and e...

Axons are the cable-like neuronal processes wiring the nervous system. They contain parallel bundles of microtubules as structural backbones, surrounded by regularly-spaced actin rings termed the periodic membrane skeleton (PMS). Despite being an evolutionarily-conserved, ubiquitous, highly-ordered feature of axons, the function of PMS is unknown....

This talk is for the workshop ”Resources Supporting the Drosophila Research Ecosystem” held Feb 17-19 at the HHMI Janelia Research Campus. Its purpose is: (1) to explain the rationale and need for proactive science communication promoting an understanding of the enormous importance of fruit fly research for modern biomedical research; (2) to descri...

The cytoskeleton is a dynamic network of filamentous protein polymers required for virtually all cellular processes. It consists of three major classes, filamentous actin (F-actin), intermediate filaments, and microtubules, all displaying characteristic structural properties, functions, cellular distributions, and sets of interacting regulatory pro...

For a long time, invertebrate model organisms such as Drosophila were essential drivers of biological research, uniquely accessible to the efficient use of genetic strategies. However, the advent of powerful scientific innovations including imaging, omics, CRISPR/Cas9 and other genetic technologies has boosted research in higher animals, and increa...

Science outreach has become increasingly important for researchers and needs to be of ever improving quality, although the time available aside our science, teaching and administration activities is steadily decreasing. To square this circle, effective strategies are required. Here we argue that this can be achieved by setting simple but ambitious...

The advent of "omic" technologies has revolutionized Genetics and created a demand to focus classical genetics on its present-day applications (Redfield, 2012, PLoS Biol 10, e1001356ff.). This demand can be met by training students in Drosophila mating scheme design, which is an important problem solving skill routinely applied in many modern resea...

Axons act like cables, electrically wiring the nervous system. Polar bundles of microtubules (MTs) form their backbones and drive their growth. Plus-end tracking proteins (+TIPs) regulate MT growth dynamics and directionality at their plus ends. However, current knowledge about +TIP functions, mostly derived from work in vitro and in non-neuronal c...

Outreach activities become an increasingly important part of a researcher's life, out of social responsibility as well as to meet expectations by research funding institutions. Yet, outreach activities are little supported by resources which provide guidance, strategies, examples and materials, and researchers are widely left alone with the task of...

The hallmarks of neurons are their slender axons which represent the longest cellular processes of animals and which act as the cables that electrically wire the brain, and the brain to the body. Axons extend along reproducible paths during development and regeneration, and they have to be maintained for the life time of an organism. Both axon exte...

http://www.frontiersin.org/Journal/FullText.aspx?s=1254&name=evolutionary_and_population_genetics&ART_DOI=10.3389/fgene.2013.00147

The extension of long slender axons is a key process of neuronal circuit formation, both during brain development and regeneration. For this, growth cones at the tips of axons are guided towards their correct target cells by signals. Growth cone behaviour downstream of these signals is implemented by their actin and microtubule cytoskeleton. In the...

2nd year Drosophila developmental genetics practical This is the teaching material for the Drosophila module of the Developmental Genetics RSM (research skills module) held at the Faculty of Life Sciences at The University of Manchester in 2013. This practical course runs over 6 days and is organised and supervised by Andreas Prokop. This module ha...

Drosophila melanogaster is a powerful model organism for biological research. The essential and common instrument of fly research is genetics, the art of applying Mendelian rules in the specific context of Drosophila with its unique classical genetic tools and the breadth of modern genetic tools and strategies brought in by molecular biology, trans...

The formation of neuronal circuits is a key process of development, laying foundations for behavior. The cellular mechanisms regulating circuit development are not fully understood. Here, we reveal Psidin as an intracellular regulator of Drosophila olfactory system formation. We show that Psidin is required in several classes of olfactory receptor...

Axon guidance is a key process during nervous system development and regeneration. One of the best established paradigms to study the mechanisms underlying this process is the axon decision of whether or not to cross the midline in the Drosophila CNS. An essential regulator of that decision is the well conserved Slit-Robo signaling pathway. Slit gu...

The correct outgrowth of axons is essential for the development and regeneration of nervous systems. Axon growth is primarily driven by microtubules. Key regulators of microtubules in this context are the spectraplakins, a family of evolutionarily conserved actin-microtubule linkers. Loss of function of the mouse spectraplakin ACF7 or of its close...

For many decades, primary neuron cultures of Drosophila have been used complementary to work in vivo. Primary cultures were instrumental for the analysis of physiological properties of Drosophila neurons and synapses, and they were used for the analysis of developmental processes. Recent developments have established Drosophila primary neurons base...

Synapse formation and maintenance crucially underlie brain function in health and disease. Both processes are believed to depend on cell adhesion molecules (CAMs). Many different classes of CAMs localise to synapses, including cadherins, protocadherins, neuroligins, neurexins, integrins, and immunoglobulin adhesion proteins, and further contributio...

Extracellular matrix (ECM) and matrix receptors are intimately involved in most biological processes. The ECM plays fundamental developmental and physiological roles in health and disease, including processes underlying the development, maintenance, and regeneration of the nervous system. To understand the principles of ECM-mediated functions in th...

The extracellular matrix (ECM) and its receptors impact the development and function of every cell type in the developing, adult and aging nervous systems. Studies on the ECM are essential to understand nervous system function in health and disease. This special issue of Developmental Neurobiology provides an overview over the enormous progress mad...

Formins are an important and evolutionarily well conserved class of actin binding proteins with essential biological functions. Although their molecular roles in actin regulation have been clearly demonstrated in vitro, their functions at the cellular or organism levels are still poorly understood. To illustrate this problem, but also to demonstrat...

Specificity of anti-Ena and anti-Chic antisera. Images show horizontal views of late embryonic CNSs (A, C, E, G, I; anterior to the left) and growth cones of primary neurons (all other images); CNSs and neurons were derived from wildtype (wt) or mutant embryos (as indicated on top) and were stained with anti-Chickadee and anti-Enabled antisera (ind...

F-actin networks are important structural determinants of cell shape and morphogenesis. They are regulated through a number of actin-binding proteins. The function of many of these proteins is well understood, but very little is known about how they cooperate and integrate their activities in cellular contexts. Here, we have focussed on the cellula...

Here we report Drosophila Waharan (Wah), a 170-kD predominantly nuclear protein with two potential human homologues, as a newly identified regulator of endosomal trafficking. Wah is required for neuromuscular-junction development and muscle integrity. In muscles, knockdown of Wah caused novel accumulations of tightly packed electron-dense tubules,...

The formation of neuronal networks, during development and regeneration, requires outgrowth of axons along reproducible paths toward their appropriate postsynaptic target cells. Axonal extension occurs at growth cones (GCs) at the tips of axons. GC advance and navigation requires the activity of their cytoskeletal networks, comprising filamentous a...

Spectraplakins are large actin-microtubule linker molecules implicated in various processes, including gastrulation, wound healing, skin blistering and neuronal degeneration. Expression data for the mammalian spectraplakin ACF7 and genetic analyses of the Drosophila spectraplakin Short stop (Shot) suggest an important role during neurogenesis. Usin...

Spectraplakins are large multifunctional cytoskeletal interacting molecules implicated in various processes, including gastrulation, wound healing, skin blistering and neuronal degeneration. It has been speculated that the various functional domains and regions found in Spectraplakins are used in context-specific manners, a model which would provid...

The regulation of growth cone actin dynamics is a critical aspect of axonal growth control. Among the proteins that are directly involved in the regulation of actin dynamics, actin nucleation factors play a pivotal role by promoting the formation of novel actin filaments. However, the essential nucleation factors in developing neurons have so far n...

Tendon cells are specialized cells of the insect epidermis that connect basally attached muscle tips to the cuticle on their apical surface via prominent arrays of microtubules. Tendon cells of Drosophila have become a useful genetic model system to address questions with relevance to cell and developmental biology. Here, we use light, confocal, an...

One of the most fascinating processes during nervous system development is the establishment of stereotypic neuronal networks. An essential step in this process is the outgrowth and precise navigation (pathfinding) of axons and dendrites towards their synaptic partner cells. This phenomenon was first described more than a century ago and, over the...

Structural synapses are key regulators of information flow in neuronal networks. To understand the function and formation of neuronal circuits, the development and function of synapses have therefore been intensely studied in both vertebrate and invertebrate species. Precise descriptions of synapses and their amenability to genetic analysis in the...

This chapter discusses the organization of the cellular system in Drosophila. The abdominal efferent system of Drosophila larva is described in detail in the chapter. Capitalizing on the efferent system of the larval Drosophila abdomen as a cellular model provides molecular insights into a number of processes, such as neuronal cell specification, n...

There are several methods to dissect Drosophila larval preparations, such as pinning out the larvae with fine pins, cactus needles, or glass electrode tips to a SYLGARD®-coated dish or adhering larva to a glass slide with special adhesives. The chapter describes the use of magnetic chambers that allow repeated fine control in spreading the larval b...

Dendrites represent arborising neurites in both vertebrates and invertebrates. However, in vertebrates, dendrites develop on neuronal cell bodies, whereas in higher invertebrates, they arise from very different neuronal structures, the primary neurites, which also form the axons. Is this anatomical difference paralleled by principal developmental a...

Adhesion between epithelial cells and extracellular substrates is normally mediated through basal adhesion complexes. However, some cells also possess comparable junctions on their apical surface. Here, we describe two new Drosophila proteins, Piopio and Papillote, that are required for the link between the apical epithelial surface and the overlyi...

The phenomenon of pioneer neurons has been known for almost a century, but so far we have little insights into mechanisms and molecules involved. Here, we study the formation of the Drosophila intersegmental motor nerve (ISN). We show that aCC/RP2 and U motor neurons grow together at the leading front of the ISN. Nevertheless, aCC/RP2 neurons are t...

Neuronal plasticity relies on tightly regulated control of protein levels at synapses. One mechanism to control protein abundance is the ubiquitin-proteasome degradation system. Recent studies have implicated ubiquitin-mediated protein degradation in synaptic development, function, and plasticity, but little is known about the regulatory mechanisms...

Neurons in primary cell cultures provide important experimental possibilities complementing or substituting those in the nervous system. However, Drosophila primary cell cultures have unfortunate limitations: they lack either a range of naturally occurring cell types, or of mature physiological properties. Here, we demonstrate a strategy which supp...

Insect neurons are individually identifiable and have been used successfully to study principles of the formation and function of neuronal circuits. In the fruitfly Drosophila, studies on identifiable neurons can be combined with efficient genetic approaches. However, to capitalise on this potential for studies of circuit formation in the CNS of Dr...

Shot (previously named Kakapo), is a Drosophila Plakin family member containing both Actin binding and microtubule binding domains. In Drosophila, it is required for a wide range of processes, including axon extension, dendrite formation, axonal terminal arborization at the neuromuscular junction, tendon cell development, and adhesion of wing epith...

The presented work pioneers the embryonic Drosophila CNS for studies of the developmental regulation and function of gamma-amino butyric acid (GABA). We describe for the first time the developmental pattern of GABA in Drosophila and address underlying regulatory mechanisms. Surprisingly, and in contrast to vertebrates, detectable levels of GABA occ...

Synaptogenesis in the CNS has received far less attention than the development of neuromuscular synapses, although only central synapses allow the study of neuronal postsynaptic mechanisms and display a greater variety of structural and functional features. This neglect is attributable mainly to the enormous complexity of the CNS, which makes the v...

A family of three position-specific (PS) integrins are expressed at the Drosophila neuromuscular junction (NMJ): a beta subunit ((betaPS), expressed in both presynaptic and postsynaptic membranes, and two alpha subunits (alphaPS1, alphaPS2), expressed at least in the postsynaptic membrane. PS integrins appear at postembryonic NMJs coincident with t...