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

J Cell Biol. 2017 Jul 3;216(7):2059-2074. doi: 10.1083/jcb.201604028. Epub 2017 May 30.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Axonal Transport*
  • Female
  • HEK293 Cells
  • HSC70 Heat-Shock Proteins / genetics
  • HSC70 Heat-Shock Proteins / metabolism*
  • Hippocampus / cytology
  • Hippocampus / metabolism*
  • Humans
  • Immunoprecipitation
  • Kinetics
  • Male
  • Mass Spectrometry
  • Mice, Knockout
  • Microscopy / methods
  • Models, Biological
  • Multiprotein Complexes
  • Neurons / metabolism*
  • Protein Interaction Maps
  • Proteomics / methods
  • Rats
  • Synapsins / deficiency
  • Synapsins / genetics
  • Synapsins / metabolism*
  • Transfection


  • HSC70 Heat-Shock Proteins
  • HSPA8 protein, human
  • Hspa8 protein, mouse
  • Hspa8 protein, rat
  • Multiprotein Complexes
  • Synapsins