Involvement of SARA in Axon and Dendrite Growth

PLoS One. 2015 Sep 25;10(9):e0138792. doi: 10.1371/journal.pone.0138792. eCollection 2015.

Abstract

SARA (Smad Anchor for Receptor Activation) plays a crucial role in Rab5-mediated endocytosis in cell lines localizing to early endosomes where it regulates morphology and function. Here, we analyzed the role of SARA during neuronal development and tested whether it functions as a regulator of endocytic trafficking of selected axonal and membrane proteins. Suppression of SARA perturbs the appearance of juxtanuclear endocytic recycling compartments and the neurons show long axons with large growth cones. Furthermore, surface distribution of the cell adhesion molecule L1 in axons and the fusion of vesicles containing transferring receptor (TfR) in dendrites were increased in neurons where SARA was silenced. Conversely, SARA overexpression generated large early endosomes and reduced neurite outgrowth. Taken together, our findings suggest a significant contribution of SARA to key aspects of neuronal development, including neurite formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Axons / metabolism*
  • Cells, Cultured
  • Dendrites / metabolism*
  • Endocytosis
  • Neural Cell Adhesion Molecule L1 / metabolism
  • Neurogenesis*
  • Rats
  • Receptors, Transferrin / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Neural Cell Adhesion Molecule L1
  • Receptors, Transferrin
  • Zfyve9 protein, rat

Grants and funding

This work was supported by grants from FONCyT (Argentina): PICT 2008-0671 to CC and PICT V 2010-1277 and Agencia Cordoba Ciencia (Argentina) to A. Cáceres and CC. CIA and SOS hold a doctoral fellowship from CONICET (Argentina).