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

AuthorsHiguero, Alonso M. ; Sánchez-Ruiloba, Lucía; Portillo, Francisco ; Iglesias, Teresa
Issue Date2010
PublisherAmerican Society for Biochemistry and Molecular Biology
CitationJournal of Biological Chemistry 285(2): 1343-1357 (2010)
AbstractIn 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.
Identifiersdoi: 10.1074/jbc.M109.024703
issn: 0021-9258
e-issn: 1083-351X
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