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

LUCAS J. SOSA; JAMES S. MALTER; J. S., HU; FLORENTYNA BUSTOS PLONKA; MARIANA OKSDATH; ALVARO NIETO GUIL; SANTIAGO QUIROGA; KARL H PFENNINGER

JOURNAL OF NEUROCHEMISTRY

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2016

0022-3042

Axonal growth cone motility requires precise regulation of adhesion in order to navigate the complex environment of the nervous system and reach its target. MARCKS (Myristoylated Alanine Rich C Kinase Substrate) 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 mis-regulation of MARCKS-P and alterations of neuronal adhesion.