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Growth cone morphology and spreading are regulated by a dynamin‐cortactin complex at point contacts in hippocampal neurons
Author(s) -
Kurklinsky Svetlana,
Chen Jing,
McNiven Mark A.
Publication year - 2011
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2011.07169.x
Subject(s) - cortactin , hippocampal formation , dynamin , morphology (biology) , neuroscience , cone (formal languages) , growth cone , biology , microbiology and biotechnology , zoology , computer science , receptor , endocytosis , genetics , axon , cytoskeleton , cell , algorithm
J. Neurochem. (2011) 117 , 48–60. Abstract Neuronal growth cone (GC) migration and targeting are essential processes for the formation of a neural network during embryonic development. Currently, the mechanisms that support directed motility of GCs are not fully defined. The large GTPase dynamin and an interacting actin‐binding protein, cortactin, have been localized to GCs, although the function performed by this complex is unclear. We have found that cortactin and the ubiquitous form of dynamin (Dyn) 2 exhibit a striking co‐localization at the base of the transition zone of advancing GCs of embryonic hippocampal neurons. Confocal and total internal reflection fluorescence microscopies demonstrate that this basal localization represents point contacts. Exogenous expression of wild‐type Dyn2 and cortactin leads to large, exceptionally flat, and static GCs, whereas disrupting this complex has no such effect. We find that excessive GC spreading is induced by Dyn2 and cortactin over‐expression and substantial recruitment of the point contact‐associated, actin‐binding protein α‐actinin1 to the ventral GC membrane. The distributions of other point contact proteins such as vinculin or paxillin appear unchanged. Immunoprecipitation experiments show that both Dyn2 and cortactin reside in a complex with α‐actinin1. These findings provide new insights into the role of Dyn2 and the actin cytoskeleton in GC adhesion and motility.