Kidins220/ARMS modulates the activity of microtubule-regulating proteins and controls neuronal polarity and development.
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.
Higuero
Alonso M
AM
Instituto de Investigaciones Biomédicas de Madrid Alberto Sols, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Madrid 28029, Spain.
Sánchez-Ruiloba
Lucía
L
Doglio
Laura E
LE
Portillo
Francisco
F
Abad-Rodríguez
José
J
Dotti
Carlos G
CG
Iglesias
Teresa
T
D000818:Animals; D016764:Cell Polarity / Q000502:physiology*; D055785:Gene Knockdown Techniques; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D016716:PC12 Cells; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000378:metabolism; D050777:Stathmin / Q000235:genetics / Q000378:metabolism; D014404:Tubulin / Q000235:genetics / Q000378:metabolism*
C418610:Kidins220 protein, rat; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D010750:Phosphoproteins; D017475:Receptors, Nerve Growth Factor; D050777:Stathmin; D014404:Tubulin; C085284:microtubule-associated protein 1B; C061082:Stmn1 protein, rat; C089212:protein kinase D; D011493:Protein Kinase C