Hsc70 chaperone activity is required for the cytosolic slow axonal transport of synapsin.

Soluble cytosolic proteins vital to axonal and presynaptic function are synthesized in the neuronal soma and conveyed via slow axonal transport. Our previous studies suggest that the overall slow transport of synapsin is mediated by dynamic assembly/disassembly of cargo complexes followed by short-range vectorial transit (the "dynamic recruitment" model). However, neither the composition of these complexes nor the mechanistic basis for the dynamic behavior is understood. In this study, we first examined putative cargo complexes associated with synapsin using coimmunoprecipitation and multidimensional protein identification technology mass spectrometry (MS). MS data indicate that synapsin is part of a multiprotein complex enriched in chaperones/cochaperones including Hsc70. Axonal synapsin-Hsc70 coclusters are also visualized by two-color superresolution microscopy. Inhibition of Hsc70 ATPase activity blocked the slow transport of synapsin, disrupted axonal synapsin organization, and attenuated Hsc70-synapsin associations, advocating a model where Hsc70 activity dynamically clusters cytosolic proteins into cargo complexes, allowing transport. Collectively, our study offers insight into the molecular organization of cytosolic transport complexes and identifies a novel regulator of slow transport. © 2017 Ganguly et al.

Citation

Archan Ganguly, Xuemei Han, Utpal Das, Lina Wang, Jonathan Loi, Jichao Sun, Daniel Gitler, Ghislaine Caillol, Christophe Leterrier, John R Yates, Subhojit Roy. Hsc70 chaperone activity is required for the cytosolic slow axonal transport of synapsin. The Journal of cell biology. 2017 Jul 03;216(7):2059-2074

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PMID: 28559423

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