Besse, F. et al. The Ig cell adhesion molecule Basigin controls compartmentalization and vesicle release at Drosophila melanogaster synapses. J. Cell Biol. 177, 843-855

Developmental Biology Unit, European Molecular Biology Laboratory, D-69117 Heidelberg, Germany.
The Journal of Cell Biology (Impact Factor: 9.83). 07/2007; 177(5):843-55. DOI: 10.1083/jcb.200701111
Source: PubMed


Synapses can undergo rapid changes in size as well as in their vesicle release function during both plasticity processes and development. This fundamental property of neuronal cells requires the coordinated rearrangement of synaptic membranes and their associated cytoskeleton, yet remarkably little is known of how this coupling is achieved. In a GFP exon-trap screen, we identified Drosophila melanogaster Basigin (Bsg) as an immunoglobulin domain-containing transmembrane protein accumulating at periactive zones of neuromuscular junctions. Bsg is required pre- and postsynaptically to restrict synaptic bouton size, its juxtamembrane cytoplasmic residues being important for that function. Bsg controls different aspects of synaptic structure, including distribution of synaptic vesicles and organization of the presynaptic cortical actin cytoskeleton. Strikingly, bsg function is also required specifically within the presynaptic terminal to inhibit nonsynchronized evoked vesicle release. We thus propose that Bsg is part of a transsynaptic complex regulating synaptic compartmentalization and strength, and coordinating plasma membrane and cortical organization.

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    • "In Drosophila, depletion of CD147 causes lethality and specific knockdown in the eye leads to misplaced subcellular organelles in photoreceptor cells [76]. Furthermore, CD147-depleted flies have misplaced glial cellphotoreceptor interactions and altered synaptic vesicle release [77]; these phenotypes may be secondary to a conserved YEKRRK sequence in the cytoplasmic tail [78]. Thus, data from the knockout models suggests CD147 has a multitude of functions including regulation of cytoskeletal remodeling, assembly of cell-cell interaction modules and subcellular vesicle distribution that span an array of biologic functions. "
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    ABSTRACT: Matrix metalloproteinases (MMPs) comprise a family of 23 zinc-dependent enzymes involved in various pathologic and physiologic processes. In cancer, MMPs contribute to processes from tumor initiation to establishment of distant metastases. Complex signaling and protein transport networks regulate MMP synthesis, cell surface presentation and release. Earlier attempts to disrupt MMP activity in patients have proven to be intolerable and with underwhelming clinical efficacy; thus targeting ancillary proteins that regulate MMP activity may be a useful therapeutic approach. EMMPRIN was originally characterized as a factor present on lung cancer cells, which stimulated collagenase (MMP-1) production in fibroblasts. Subsequent studies demonstrated that EMMPRIN was identical to several other protein factors, including basigin, all of which are now commonly termed CD147. CD147 modulates the synthesis and activity of soluble and membrane-bound (MT-MMPs) in various contexts via homophilic/heterophilic cell interactions, vesicular shedding or cell-autonomous processes. CD147 also participates in inflammation, nutrient and drug transporter activity, microbial pathology and developmental processes. Despite the hundreds of manuscripts demonstrating CD147-mediated MMP regulation, the molecular underpinnings governing this process have not been fully elucidated. The present review summarizes our present knowledge of the complex regulatory systems influencing CD147 biology and provides a framework to understand how CD147 may influence MMP activity.
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    • "These observations provide an insight into the indispensable role of EMMPRIN in normal CNS physiology. In this context, a study on Drosophila melanogaster showed that EMMPRIN was vital for proper synaptic functioning, including distribution of synaptic vesicles and their release at the neuromuscular junctions [41]. As these findings highlight numerous roles for EMMPRIN in the CNS, it is logical that diseases of the CNS would present with EMMPRIN deregulation. "
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    ABSTRACT: Matrix metalloproteinases (MMPs) are engaged in pathologies associated with infections, tumors, autoimmune disorders and neurological dysfunctions. With the identification of an upstream regulator of MMPs, EMMPRIN (Extracellular matrix metalloproteinase inducer, CD147), it is relevant to address if EMMPRIN plays a role in the pathology of central nervous system (CNS) diseases. This would enable the possibility of a more upstream and effective therapeutic target. Indeed, conditions including gliomas, Alzheimer’s disease (AD), multiple sclerosis (MS), and other insults such as hypoxia/ischemia show elevated levels of EMMPRIN which correlate with MMP production. In contrast, given EMMPRIN’s role in CNS homeostasis with respect to regulation of monocarboxylate transporters (MCTs) and interactions with adhesion molecules including integrins, we need to consider that EMMPRIN may also serve important regulatory or protective functions. This review summarizes the current understanding of EMMPRIN’s involvement in CNS homeostasis, its possible roles in escalating or reducing neural injury, and the mechanisms of EMMPRIN including and apart from MMP induction.
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    • "When the BRP immunostaining at the neuromuscular junction was observed with the electron microscope, it appeared exclusively at synapses [12]. Double staining for nc82 and antibodies specific for glutamate receptors defined that practically each BRP-spot (presynaptic side of a single synapse) correlated with a single cluster of glutamate receptors (postsynaptic side of the same synapse) reinforcing the view that anti-BRP alone can be used to obtain a good estimation of synapse numbers [12], [15], [36], [38], [39], [43], [46]–[48], [50]. "
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    ABSTRACT: Previous studies have shown that the morphology of the neuromuscular junction of the flight motor neuron MN5 in Drosophila melanogaster undergoes daily rhythmical changes, with smaller synaptic boutons during the night, when the fly is resting, than during the day, when the fly is active. With electron microscopy and laser confocal microscopy, we searched for a rhythmic change in synapse numbers in this neuron, both under light:darkness (LD) cycles and constant darkness (DD). We expected the number of synapses to increase during the morning, when the fly has an intense phase of locomotion activity under LD and DD. Surprisingly, only our DD data were consistent with this hypothesis. In LD, we found more synapses at midnight than at midday. We propose that under LD conditions, there is a daily rhythm of formation of new synapses in the dark phase, when the fly is resting, and disassembly over the light phase, when the fly is active. Several parameters appeared to be light dependent, since they were affected differently under LD or DD. The great majority of boutons containing synapses had only one and very few had either two or more, with a 70∶25∶5 ratio (one, two and three or more synapses) in LD and 75∶20∶5 in DD. Given the maintenance of this proportion even when both bouton and synapse numbers changed with time, we suggest that there is a homeostatic mechanism regulating synapse distribution among MN5 boutons.
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