Folma Buss

Folma Buss
University of Cambridge | Cam · Cambridge Institute for Medical Research

PhD

About

121
Publications
11,001
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4,827
Citations
Citations since 2017
32 Research Items
2001 Citations
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2017201820192020202120222023050100150200250300
2017201820192020202120222023050100150200250300
2017201820192020202120222023050100150200250300
Additional affiliations
February 1995 - present
University of Cambridge
Position
  • Professor (Full)

Publications

Publications (121)
Article
Full-text available
Unconventional myosins are a superfamily of actin-based motor proteins that perform a number of roles in fundamental cellular processes, including (but not limited to) intracellular trafficking, cell motility, endocytosis, exocytosis and cytokinesis. 40 myosins genes have been identified in humans, which belong to different 12 classes based on thei...
Article
Full-text available
Mitochondria are multifunctional organelles that not only produce energy for the cell, but are also important for cell signalling, apoptosis and many biosynthetic pathways. In most cell types, they form highly dynamic networks that are constantly remodelled through fission and fusion events, repositioned by motor-dependent transport and degraded wh...
Article
Full-text available
Spermiogenesis is the final stage of spermatogenesis, a differentiation process during which unpolarized spermatids undergo excessive remodeling that results in the formation of sperm. The actin cytoskeleton and associated actin-binding proteins play crucial roles during this process regulating organelle or vesicle delivery/segregation and forming...
Chapter
Given the prevalence and importance of the actin cytoskeleton and the host of associated myosin motors, it comes as no surprise to find that they are linked to a plethora of cellular functions and pathologies. Although our understanding of the biophysical properties of myosin motors has been aided by the high levels of conservation in their motor d...
Article
Full-text available
During spermiogenesis in mammals actin filaments and a variety of actin-binding proteins are involved in the formation and function of highly specialized testis-specific structures. Actin-based motor proteins, such as myosin Va and VIIa, play a key role in this complex process of spermatid transformation into mature sperm. We have previously demons...
Article
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Optineurin (OPTN) is a multifunctional protein involved in autophagy, secretion as well as NF-κB and IRF3 signalling and OPTN mutations are associated with several human diseases. Here we show that, in response to viral RNA, OPTN translocates to foci in the perinuclear region, where it negatively regulates NF-κB and IRF3 signalling pathways and dow...
Article
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Autophagy defends cells against proliferation of bacteria such as Salmonella in the cytosol. After escape from a damaged Salmonella-containing vacuole (SCV) exposing luminal glycans that bind to Galectin-8, the host cell ubiquitination machinery deposits a dense layer of ubiquitin around the cytosolic bacteria. The nature and spatial distribution o...
Article
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Myosin VI (MYO6) is an actin-based motor that has been implicated in a wide range of cellular processes, including endocytosis and the regulation of actin dynamics. MYO6 is crucial for actin/membrane remodeling during the final step of Drosophila spermatogenesis, and MYO6-deficient males are sterile. This protein also localizes to actin-rich struct...
Preprint
Full-text available
Optineurin (OPTN) is a multifunctional protein involved in autophagy, secretion as well as NF-κB and IRF3 signalling and mutations are associated with several human diseases including primary open-angle glaucoma (POAG), amyotrophic lateral sclerosis (ALS), Paget’s disease of bone (PDB) and Crohn’s disease (CD). Here we show that, in response to vir...
Article
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The dynamics and coordination between autophagy machinery and selective receptors during mitophagy are unknown. Also unknown is whether mitophagy depends on pre-existing membranes or is triggered on the surface of damaged mitochondria. Using a ubiquitin-dependent mitophagy inducer, the lactone ivermectin, we have combined genetic and imaging experi...
Article
Myosins of class VI (MYO6) are unique actin‐based motor proteins that move cargo towards the minus ends of actin filaments. As the sole myosin with this directionality, it is critically important in a number of biological processes. Indeed, loss or overexpression of MYO6 in humans is linked to a variety of pathologies including deafness, cardiomyop...
Article
Mitochondrial homeostasis is maintained by removing dysfunctional, ubiquitinated mitochondria from the network via PRKN-dependent mitophagy. MYO6, a unique myosin that moves towards the minus ends of actin filaments, forms a complex with PRKN and is selectively recruited to damaged mitochondria by binding to ubiquitin. On the mitochondrial surface,...
Article
Full-text available
The intracellular functions of myosin motors requires a number of adaptor molecules, which control cargo attachment, but also fine-tune motor activity in time and space. These motor-adaptor-cargo interactions are often weak, transient or highly regulated. To overcome these problems, we use a proximity labelling-based proteomics strategy to map the...
Article
Full-text available
Mitochondrial quality control is essential to maintain cellular homeostasis and is achieved by removing damaged, ubiquitinated mitochondria via Parkin-mediated mitophagy. Here, we demonstrate that MYO6 (myosin VI), a unique myosin that moves toward the minus end of actin filaments, forms a complex with Parkin and is selectively recruited to damaged...
Article
Mitochondrial quality control is essential to maintain cellular homeostasis and is achieved by removing damaged, ubiquitinated mitochondria via Parkin-mediated mitophagy. Here, we demonstrate that MYO6 (myosin VI), a unique myosin that moves towards the minus end of actin filaments, forms a complex with Parkin and is selectively recruited to damage...
Article
Full-text available
APPL1- and RAB5-positive signaling endosomes play a crucial role in the activation of AKT in response to extracellular stimuli. Myosin VI (MYO6) and two of its cargo adaptor proteins, GIPC and TOM1/TOM1L2, localize to these peripheral endosomes and mediate endosome association with cortical actin filaments. Loss of MYO6 leads to the displacement of...
Article
APPL1- and RAB5-positive signaling endosomes play a crucial role in the activation of AKT in response to extracellular stimuli. Myosin VI (MYO6) and two of its cargo adaptor proteins, GIPC and TOM1/TOM1L2, localize to these peripheral endosomes and mediate endosome association with cortical actin filaments. Loss of MYO6 leads to the displacement of...
Article
To establish infections, $\textit{Salmonella}$ injects virulence effectors that hijack the host actin cytoskeleton and phosphoinositide signaling to drive pathogen invasion. How effectors reprogram the cytoskeleton network remains unclear. By reconstituting the activities of the $\textit{Salmonella}$ effector SopE, we recapitulated Rho GTPase-drive...
Article
In this chapter we describe the use of correlative light-electron microscopy (CLEM) to study, in cultured cells, the turnover of damaged mitochondria by PINK1/Parkin-dependent mitophagy. CLEM combines the advantages of light microscopy, which allows to image and rapidly screen a large number of the cells, while electron microscopy provides high-res...
Article
In this study, we demonstrate myosin VI enrichment at Cx43 (also known as GJA1)-containing gap junctions (GJs) in heart tissue, primary cardiomyocytes and cell culture models. In primary cardiac tissue and in fibroblasts from the myosin VI-null mouse as well as in tissue culture cells transfected with siRNA against myosin VI, we observe reduced GJ...
Article
Full-text available
Significance Salmonella causes many different diseases including gastroenteritis and typhoid fever. For infection to take place, Salmonella must enter the epithelium in the gut by injecting a number of effector proteins that trigger dramatic actin rearrangements and membrane ruffles to engulf the pathogen. In this study we identified a myosin motor...
Article
Myosin VI (MYO6) is the only myosin known to move toward the minus end of actin filaments. It has roles in numerous cellular processes, including maintenance of stereocilia structure, endocytosis, and autophagosome maturation. However, the functional necessity of minus-end-directed movement along actin is unclear as the underlying architecture of t...
Article
Significance How the mechanical properties of myosin motors relate to their functions in cells is poorly understood. Myosin VI (MYO6) is the only myosin that moves to the minus end of actin filaments, but the cellular requirement of this reverse movement is unknown. To investigate this question, we generated a mechanical mutant of MYO6, MYO6+, whic...
Article
Full-text available
In this study, we demonstrate myosin VI enrichment at Cx43 gap junctions in heart tissue, primary cardiomyocytes and cell culture models. The loss of myosin VI via siRNA-mediated knock down or isolation of primary cardiac tissue and fibroblasts from the myosin VI-null mouse results in reduced GJ plaque size with a concomitant reduction in intercell...
Chapter
Myosins are cytoskeletal motor proteins that use energy derived from ATP hydrolysis to generate force and movement along actin filaments. Humans express 38 myosin genes belonging to 12 classes that participate in a diverse range of crucial activities, including muscle contraction, intracellular trafficking, cell division, motility, actin cytoskelet...
Article
Full-text available
Mutations in myosin VI have been associated with autosomal recessive (DFNB37) and autosomal dominant (DFNA22) deafness in humans. Here, we characterise a myosin VI nonsense mutation (R1166X) that was identified in a family with hereditary hearing loss in Pakistan. This mutation leads to deletion of the C-terminal 120 amino acids of the myosin VI ca...
Article
Full-text available
Myosin motor proteins working together with the actin cytoskeleton drive a wide range of cellular processes. In this review, we focus on their roles in autophagy – the pathway the cell uses to ensure homeostasis by targeting pathogens, misfolded proteins and damaged organelles for degradation. The actin cytoskeleton regulated by a host of nucleatin...
Article
This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1111/tra.12405
Article
Full-text available
Myosin motor proteins working together with the actin cytoskeleton drive a wide range of cellular processes. In this review, we focus on their roles in autophagy - the pathway the cell uses to ensure homeostasis by targeting pathogens, misfolded proteins and damaged organelles for degradation. The actin cytoskeleton regulated by a host of nucleatin...
Article
Full-text available
The myosins are a large family of actin-binding motor proteins that convert stored chemical energy into work, with important functions in intracellular transport, force generation, and mechanosensation (1). Despite many advances in understanding the mechanical and kinetic properties of purified myosins in vitro, the signals that regulate the functi...
Article
Full-text available
Autophagy plays a key role during Salmonella infection, by eliminating these pathogens following escape into the cytosol. In this process, selective autophagy receptors, including the myosin VI adaptor proteins optineurin and NDP52, have been shown to recognize cytosolic pathogens. Here, we demonstrate that myosin VI and TAX1BP1 are recruited to ub...
Article
Full-text available
Myo1c, a single-­‐headed myosin of class I, associates with cholesterol-­enriched lipid rafts and facilitates their recycling from intracellular compartments to the cell surface. Absence of functional Myo1c disturbs the cellular distribution of lipid rafts, causes the accumulation of cholesterol‐enriched membranes in the perinuclear recycling compa...
Article
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Huntingtin is a large membrane associated scaffolding protein that associates with endocytic and exocytic vesicles and modulates their trafficking along cytoskeletal tracks. Although Huntington's disease progression is linked to toxic accumulation of mutant huntingtin protein, loss of wildtype huntingtin function may also contribute to neuronal cel...
Article
Full-text available
The coordinated trafficking and tethering of membrane cargo within cells relies on the function of distinct cytoskeletal motors that are targeted to specific subcellular compartments through interactions with protein adaptors and phospholipids. The unique actin motor myosin VI functions at distinct steps during clathrin-mediated endocytosis and the...
Article
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Before undergoing neuroexocytosis, secretory granules (SGs) are mobilized and tethered to the cortical actin network by an unknown mechanism. Using an SG pull-down assay and mass spectrometry, we found that myosin VI was recruited to SGs in a Ca(2+)-dependent manner. Interfering with myosin VI function in PC12 cells reduced the density of SGs near...
Article
Full-text available
Advances in screening and computational methods have enhanced recent efforts to discover/design small-molecule protein inhibitors. One attractive target for inhibition is the myosin family of motor proteins. Myosins function in a wide variety of cellular processes, from intracellular trafficking to cell motility, and are implicated in several human...
Article
Full-text available
Autophagy targets pathogens, damaged organelles and protein aggregates for lysosomal degradation. These ubiquitylated cargoes are recognized by specific autophagy receptors, which recruit LC3-positive membranes to form autophagosomes. Subsequently, autophagosomes fuse with endosomes and lysosomes, thus facilitating degradation of their content; how...
Article
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Cellular signaling pathways underlie the transfer of information throughout the cell and to adjoining cells and so govern most critical cellular functions. Increasing evidence points to the molecular motor myosin 1c as a prominent player in many signaling cascades, from the integrin-dependent signaling involved in cell migration to the signaling ev...
Article
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The actin-based molecular motor myosin VI functions in the endocytic uptake pathway, both during the early stages of clathrin-mediated uptake and in later transport to/from early endosomes. This study uses fluorescence recovery after photobleaching (FRAP) to examine the turnover rate of myosin VI during endocytosis. The results demonstrate that myo...
Article
Full-text available
Lipid rafts are highly dynamic membrane subdomains enriched in specific protein and lipid components that create specialized 'organizing' platforms essential for an array of important cellular functions. The role of lipid rafts in membrane trafficking involves the constant remodelling of the plasma membrane through membrane uptake and balanced exoc...
Article
Full-text available
Myosin-6 is an actin-based motor protein that moves its cargo towards the minus-end of actin filaments. Mutations in the gene encoding the myosin-6 heavy chain and changes in the cellular abundance of the protein have been linked to hypertrophic cardiomyopathy, neurodegenerative diseases, and cancer. Here, we present a detailed kinetic characteriza...
Article
Full-text available
A balance between endocytosis and membrane recycling regulates the composition and dynamics of the plasma membrane. Internalization and recycling of cholesterol- and sphingolipid-enriched lipid rafts is an actin-dependent process that is mediated by a specialized Arf6-dependent recycling pathway. Here, we identify myosin1c (Myo1c) as the first moto...
Article
The molecular motor myosin VI has been implicated in endocytosis, a trafficking pathway mediating intracellular uptake of items such as membrane receptors and nutrients. Previous studies demonstrate the localization of the large insert isoform of myosin VI to clathrin-coated vesicles and the no insert isoform of myosin VI to early endosomes. The ki...
Article
Full-text available
In eukaryotes, the final steps in both the regulated and constitutive secretory pathways can be divided into four distinct stages: (i) the 'approach' of secretory vesicles/granules to the PM (plasma membrane), (ii) the 'docking' of these vesicles/granules at the membrane itself, (iii) the 'priming' of the secretory vesicles/granules for the fusion...
Article
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Here, we report that the natural compound pentachloropseudilin (PClP) acts as a reversible and allosteric inhibitor of myosin ATPase and motor activity. IC50 values are in the range from 1 to 5 μm for mammalian class-1 myosins and greater than 90 μm for class-2 and class-5 myosins, and no inhibition was observed with class-6 and class-7 myosins. We...
Article
Full-text available
In humans, a vast array of cytoskeletal motor proteins (19 dyneins, 43 kinesins, and 39 myosins) (1) move along microtubule and actin filament tracks to generate an enormous range of cellular functions. The kinesin and dynein motor proteins drive long-distance transport along microtubules, whereas the myosins are responsible for short-range deliver...
Article
Full-text available
During constitutive secretion, proteins synthesized at the endoplasmic reticulum (ER) are transported to the Golgi complex for processing and then to the plasma membrane for incorporation or extracellular release. This study uses a unique live-cell constitutive secretion assay to establish roles for the molecular motor myosin VI and its binding par...
Article
Full-text available
The polarized trafficking of membrane proteins into the leading edge of the cell is an integral requirement for cell migration. Myosin VI and its interacting protein optineurin have previously been shown to operate in anterograde trafficking pathways, especially for the polarized delivery of cargo to the basolateral domain in epithelial cells. Here...