Kidins220/ARMS modulates the activity of microtubule-regulating proteins and controls neuronal polarity and development

J Biol Chem. 2010 Jan 8;285(2):1343-57. doi: 10.1074/jbc.M109.024703. Epub 2009 Nov 10.


In order for neurons to perform their function, they must establish a highly polarized morphology characterized, in most of the cases, by a single axon and multiple dendrites. Herein we find that the evolutionarily conserved protein Kidins220 (kinase D-interacting substrate of 220-kDa), also known as ARMS (ankyrin repeat-rich membrane spanning), a downstream effector of protein kinase D and neurotrophin and ephrin receptors, regulates the establishment of neuronal polarity and development of dendrites. Kidins220/ARMS gain and loss of function experiments render severe phenotypic changes in the processes extended by hippocampal neurons in culture. Although Kidins220/ARMS early overexpression hinders neuronal development, its down-regulation by RNA interference results in the appearance of multiple longer axon-like extensions as well as aberrant dendritic arbors. We also find that Kidins220/ARMS interacts with tubulin and microtubule-regulating molecules whose role in neuronal morphogenesis is well established (microtubule-associated proteins 1b, 1a, and 2 and two members of the stathmin family). Importantly, neurons where Kidins220/ARMS has been knocked down register changes in the phosphorylation activity of MAP1b and stathmins. Altogether, our results indicate that Kidins220/ARMS is a key modulator of the activity of microtubule-regulating proteins known to actively regulate neuronal morphogenesis and suggest a mechanism by which it contributes to control neuronal development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Polarity / physiology*
  • Gene Knockdown Techniques
  • Hippocampus / cytology
  • Hippocampus / metabolism*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism*
  • Neurons / cytology
  • Neurons / metabolism*
  • PC12 Cells
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • Protein Kinase C / genetics
  • Protein Kinase C / metabolism
  • Rats
  • Receptors, Nerve Growth Factor / genetics
  • Receptors, Nerve Growth Factor / metabolism
  • Stathmin / genetics
  • Stathmin / metabolism
  • Tubulin / genetics
  • Tubulin / metabolism*


  • Kidins220 protein, rat
  • Membrane Proteins
  • Microtubule-Associated Proteins
  • Phosphoproteins
  • Receptors, Nerve Growth Factor
  • Stathmin
  • Tubulin
  • microtubule-associated protein 1B
  • Stmn1 protein, rat
  • protein kinase D
  • Protein Kinase C