CMS/CD2AP is a cytoplasmic protein critical for the integrity of the kidney glomerular filtration and the T cell function. CMS contains domains and motifs characteristic for protein-protein interactions, and it is inv...
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CMS/CD2AP is a cytoplasmic protein critical for the integrity of the kidney glomerular filtration and the T cell function. CMS contains domains and motifs characteristic for protein-protein interactions, and it is involved in the regulation of the actin cytoskeleton, We report here that the individual SH3 domains of CMS bind to phosphotyrosine proteins of similar to 80, 90, and 180 kDa in cell lysates stimulated with epidermal growth factor. The second SH3 domain of CMS bound specifically to a tyrosine-phosphorylated protein of 120 kDa, which we identified as the proto-oncoprotein c-Cbl. The c-Cbl-binding site for CMS mapped to the carboxyl terminus of c-Cbl and is different from the proline-rich region known to bind SH3-containing proteins. CMS binding to c-Cbl was markedly attenuated in a tyrosine phosphorylation-defective c-Cbl mutant indicating that this interaction is dependent on the tyrosine phosphorylation of CMS. It also implies that CMS interacts with c-Cbl in an inducible fashion upon stimulation of a variety of cell-surface receptors. Immunofluorescence analysis revealed that both proteins colocalize at lamellipodia and leading edges of cells, and we propose that the interaction of CMS with c-Cbl offers a mechanism by which c-Cbl associates and regulates the actin cytoskeleton.
Precise synaptogenesis is crucial to brain development, and depends on the ability of specific partner cells to locate and communicate with one another. Dynamic properties of axonal filopodia during synaptic targeting...
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Precise synaptogenesis is crucial to brain development, and depends on the ability of specific partner cells to locate and communicate with one another. Dynamic properties of axonal filopodia during synaptic targeting are well documented, but the cytomorphological dynamics of postsynaptic cells have received less attention. In Drosophila embryos, muscle cells bear numerous postsynaptic filopodia ('myopodia') during motoneuron targeting. Here we show that myopodia are actin-filled microprocesses, which progressively clustered at the site of motoneuron innervation while intermingling with presynaptic filopodia. In prospero mutants, which have severe delays in axon outgrowth from the CNS, myopodia were present initially but clustering behavior was not observed, demonstrating that clustering depends on innervating axons. Thus, postsynaptic filopodia are capable of intimate interaction with innervating presynaptic axons. We propose that, by contributing to direct long-distance cellular communication, they are dynamically involved in synaptic matchmaking.
We used time-lapse fluorescence microscopy to observe the growth of Mauthner cell axone and their postsynaptic targets, the primary motor neurons, in spinal cords of developing zebrafish embryos. Upon reaching success...
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We used time-lapse fluorescence microscopy to observe the growth of Mauthner cell axone and their postsynaptic targets, the primary motor neurons, in spinal cords of developing zebrafish embryos. Upon reaching successive motor neurons, the Mauthner growth cone paused briefly before continuing along its path. Varicosities formed at regular intervals and were preferentially associated with the target regions of the primary motor neurons. In addition, the postsynaptic motor neurons showed highly dynamic filopodia, which transiently interacted with both the growth cone and the axon. Both Mauthner cell and motor neurons were highly active, each showing motility sufficient to initiate synaptogenesis.
We have previously shown that the glycosylphosphatidyl-inositol (GPI)-linked urokinase-type plasminogen activator receptor (uPAR) reversibly associates with the integrins complement receptor type 3 (CR3;α(M)β2) and ...
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We have previously shown that the glycosylphosphatidyl-inositol (GPI)-linked urokinase-type plasminogen activator receptor (uPAR) reversibly associates with the integrins complement receptor type 3 (CR3;α(M)β2) and CR4 (α(X)β2) during leukocyte motility. These receptor-to-receptor interactions could potentially be accounted for by diffusion-controlled reactions or by directed transport phenomena. To address these alternatives, we have used computer simulation techniques. Our results show that a diffusion-controlled interaction between uPAR and CR4 during accumulation at lamellipodia is not physically reasonable. This suggests that a directed transport mechanism participates in establishing uPAR-integrin association.
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