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Interactions between the L1 cell adhesion molecule and ezrin support traction‐force generation and can be regulated by tyrosine phosphorylation
Author(s) -
Sakurai Takeshi,
Gil Orlando D.,
Whittard John D.,
Gazdoiu Mihaela,
Joseph Todd,
Wu James,
Waksman Adam,
Benson Deanna L.,
Salton Stephen R.,
Felsenfeld Dan P.
Publication year - 2008
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.21705
Subject(s) - ezrin , microbiology and biotechnology , ferm domain , tyrosine phosphorylation , phosphorylation , cytoskeleton , proto oncogene tyrosine protein kinase src , cell adhesion , biology , l1 , actin cytoskeleton , chemistry , membrane protein , biochemistry , cell , integral membrane protein , membrane , gene
An Ig superfamily cell‐adhesion molecule, L1, forms an adhesion complex at the cell membrane containing both signaling molecules and cytoskeletal proteins. This complex mediates the transduction of extracellular signals and generates actin‐mediated traction forces, both of which support axon outgrowth. The L1 cytoplasmic region binds ezrin, an adapter protein that interacts with the actin cytoskeleton. In this study, we analyzed L1–ezrin interactions in detail, assessed their role in generating traction forces by L1, and identified potential regulatory mechanisms controlling ezrin–L1 interactions. The FERM domain of ezrin binds to the juxtamembrane region of L1, demonstrated by yeast two‐hybrid interaction traps and protein binding analyses in vitro. A lysine‐to‐leucine substitution in this domain of L1 (K1147L) shows reduced binding to the ezrin FERM domain. Additionally, in ND7 cells, the K1147L mutation inhibits retrograde movement of L1 on the cell surface that has been linked to the generation of the traction forces necessary for axon growth. A membrane‐permeable peptide consisting of the juxtamembrane region of L1 that can disrupt endogenous L1–ezrin interactions inhibits neurite extension of cerebellar cells on L1 substrates. Moreover, the L1–ezrin interactions can be modulated by tyrosine phosphorylation of the L1 cytoplasmic region, namely, Y1151, possibly through Src‐family kinases. Replacement of this tyrosine together with Y1176 with either aspartate or phenylalanine changes ezrin binding and alters colocalization with ezrin in ND7 cells. Collectively, these data suggest that L1–ezrin interactions mediated by the L1 juxtamembrane region are involved in traction‐force generation and can be regulated by the phosphorylation of L1. © 2008 Wiley‐Liss, Inc.