Growth cone morphology and spreading are regulated by a dynamin-cortactin complex at point contacts in hippocampal neurons

Svetlana Kurklinsky, Jing Chen, Mark A. McNiven

Research output: Contribution to journalArticle

26 Citations (Scopus)

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 a-actinin1. These findings provide new insights into the role of Dyn2 and the actin cytoskeleton in GC adhesion and motility.

Original languageEnglish
Pages (from-to)48-60
Number of pages13
JournalJournal of Neurochemistry
Volume117
Issue number1
DOIs
StatePublished - 1 Apr 2011

Fingerprint

Cortactin
Dynamins
Growth Cones
Point contacts
Neurons
Cones
Microfilament Proteins
Dynamin II
Paxillin
Vinculin
Fluorescence microscopy
GTP Phosphohydrolases
Actin Cytoskeleton
Fluorescence Microscopy
Immunoprecipitation
Embryonic Development
Actins
Adhesion
Neural networks
Membranes

Keywords

  • Actin
  • Actinin
  • Cortactin
  • Dynamin
  • Growth cone
  • Hippocampus

Cite this

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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 a-actinin1. These findings provide new insights into the role of Dyn2 and the actin cytoskeleton in GC adhesion and motility.",
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Growth cone morphology and spreading are regulated by a dynamin-cortactin complex at point contacts in hippocampal neurons. / Kurklinsky, Svetlana; Chen, Jing; McNiven, Mark A.

In: Journal of Neurochemistry, Vol. 117, No. 1, 01.04.2011, p. 48-60.

Research output: Contribution to journalArticle

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