Mutation of a putative MAP kinase consensus site regulates NCAM endocytosis and NCAM-dependent neurite outgrowth

•NCAM140 is phosphorylated by ERK2.•Endocytosis of NCAM140 is regulated by MAP kinase activity.•T803D mutation regulates endocytosis and NCAM-dependent neurite growth. The cytoplasmic domain of the neural cell adhesion molecule NCAM contains several putative serine/threonine phosphorylation sites wh...

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Bibliographic Details
Published in:Neuroscience research 2017-07, Vol.120, p.28-35
Main Authors: Goschzik, Tobias, Cremer, Harold, Gnanapragassam, Vinayaga S., Horstkorte, Rüdiger, Bork, Kaya, Diestel, Simone
Format: Article
Language:English
Subjects:
Cell Adhesion Molecules, Neuronal - metabolism
Cells, Cultured
Cellular Biology
Development Biology
Endocytosis
ERK phosphorylation
Human NCAM140
Humans
Life Sciences
MAP Kinase Signaling System
Mitogen-Activated Protein Kinase 1 - metabolism
Mutation
Neurite outgrowth
Neuronal Outgrowth
Phosphorylation
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Summary:•NCAM140 is phosphorylated by ERK2.•Endocytosis of NCAM140 is regulated by MAP kinase activity.•T803D mutation regulates endocytosis and NCAM-dependent neurite growth. The cytoplasmic domain of the neural cell adhesion molecule NCAM contains several putative serine/threonine phosphorylation sites whose functions are largely unknown. Human NCAM140 (NCAM140) possesses a potential MAP kinase phosphorylation site at threonine (T) 803. The aim of this study was to analyze a possible phosphorylation of NCAM140 by MAP kinases and to identify the functional role of T803. We found that NCAM140 is phosphorylated by the MAP kinase ERK2 in vitro. Exchange of T803 to aspartic acid (D) which mimics constitutive phosphorylation at the respective position resulted in increased endocytosis compared to NCAM140 in neuroblastoma cells and primary neurons. Consistently, NCAM140 endocytosis was inhibited by the MEK inhibitor U0126 in contrast to NCAM140-T803D or NCAM140-T803A endocytosis supporting a role of a potential ERK2 mediated phosphorylation at this site in endocytosis. Furthermore, cells expressing NCAM140-T803D developed significantly shorter neurites than NCAM140 expressing cells indicating that a potential phosphorylation of NCAM by ERK2 also regulates NCAM-dependent neurite outgrowth.
ISSN:0168-0102
1872-8111
DOI:10.1016/j.neures.2017.02.002