Integrin activation and neurotrophin signaling cooperate to enhance neurite outgrowth in sensory neurons

Budd A Tucker; Masuma Rahimtula; Karen M Mearow

doi:10.1002/cne.20518

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Integrin activation and neurotrophin signaling cooperate to enhance neurite outgrowth in sensory neurons

Journal article

Peer reviewed

Integrin activation and neurotrophin signaling cooperate to enhance neurite outgrowth in sensory neurons

Budd A Tucker, Masuma Rahimtula and Karen M Mearow

Journal of comparative neurology (1911), Vol.486(3), pp.267-280

06/06/2005

DOI: 10.1002/cne.20518

PMID: 15844170

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Abstract

Neurite growth is influenced by many factors, including the availability of trophic support as well as the extracellular environment. In this study, we have investigated whether attachment to a permissive culture substrate such as laminin is sufficient to promote neurite outgrowth from dorsal root ganglion neurons in the absence of added nerve growth factor (NGF) and whether this attachment can enhance the response of these neurons to NGF. Adult dorsal root ganglia neurons plated on surfaces coated with a thin film of laminin exhibited increased neurite outgrowth. This effect was integrin-dependent as it was attenuated by treatment with RGD (arginine-glycine-aspartate) peptides and by a beta1-integrin blocking antibody. The addition of NGF resulted in a significant increase in the integrin-dependent outgrowth. We have correlated this increase in growth with increased expression of integrin subunits and activation of known downstream signaling intermediates such as focal adhesion kinase, Src, and Akt. We have also examined pathway cooperation through the use of an Src-specific inhibitor, PP2, and a beta1-integrin blocking antibody, beta1i, by observing downstream signaling intermediates in both integrin and growth factor signaling pathways. These results are among the first to detail the importance of interactions between neurotrophin- and integrin-activated signaling in adult primary neurons.

Neurites - physiology

Protein-Tyrosine Kinases - metabolism

Cell Count

Male

Ganglia, Spinal - cytology

Focal Adhesion Kinase 1

Laminin - physiology

Drug Interactions

Time Factors

Extracellular Matrix - physiology

Integrins - drug effects

Neurites - drug effects

Protein-Serine-Threonine Kinases - metabolism

Animals, Newborn

Integrins - physiology

Neurons, Afferent - drug effects

Proto-Oncogene Proteins - metabolism

Neurons, Afferent - cytology

Polylysine - physiology

Integrins - immunology

Cells, Cultured

Enzyme Inhibitors - pharmacology

Focal Adhesion Protein-Tyrosine Kinases

Nerve Growth Factor - pharmacology

Rats

Oligopeptides - metabolism

Pyrimidines - pharmacology

Cell Adhesion - drug effects

Neurons, Afferent - physiology

Rats, Sprague-Dawley

Blotting, Western

Antibodies - pharmacology

Immunohistochemistry - methods

Proto-Oncogene Proteins c-akt

Animals

Polysaccharides - physiology

Signal Transduction - drug effects

Cell Adhesion - physiology

Signal Transduction - physiology

Oligopeptides - pharmacology

Details

Title: Subtitle: Integrin activation and neurotrophin signaling cooperate to enhance neurite outgrowth in sensory neurons
Creators: Budd A Tucker - Division of Basic Medical Sciences, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador A1B 3V6, Canada
Masuma Rahimtula
Karen M Mearow
Resource Type: Journal article
Publication Details: Journal of comparative neurology (1911), Vol.486(3), pp.267-280
Publisher: United States
DOI: 10.1002/cne.20518
PMID: 15844170
ISSN: 0021-9967
eISSN: 1096-9861
Language: English
Date published: 06/06/2005
Academic Unit: Ophthalmology and Visual Sciences
Record Identifier: 9983980288302771

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