Protein interacting with NIMA (never in mitosis A)‐1 regulates axonal growth cone adhesion and spreading through myristoylated alanine‐rich C kinase substrate isomerization

Axonal growth cone motility requires precise regulation of adhesion to navigate the complex environment of the nervous system and reach its target. Myristoylated alanine‐rich C kinase substrate (MARCKS) protein is enriched in the developing brain and plays an important, phosphorylation‐dependent role in the modulation of axonal growth cone adhesion. The ratio of phospho‐MARCKS (MARCKS‐P) to total MARCKS controls adhesion modulation and spreading of the axonal growth cone. Pin1, a peptidyl‐prolyl cis/trans isomerase (PPIase) that recognizes and binds to phosphorylated serine/threonine residues preceded by a proline (pSer/Thr‐Pro) is also expressed in the developing brain. Here, we show that Pin1 is present in the growth cone, interacts with MARCKS‐P, and regulates its dephosphorylation. We also described morphological alterations in the corpus callosum and cerebral cortex fibers of the Pin1 knockout mouse brain that may be caused by the misregulation of MARCKS‐P and alterations of neuronal adhesion.

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