Abstract
The successful regeneration of peripheral branches of sensory neurons following injury is attributed to the presence of neurotrophins and interaction of regenerating axons with the extracellular matrix. Here, we show that the laminin receptor, alpha7beta1 integrin is a crucial mediator of neurite outgrowth from distinct populations of sensory neurons. Following sciatic nerve crush, alpha7 integrin is expressed by medium-large diameter, NF200-immunoreactive (IR), and medium diameter, CGRP-IR, neurons, but very few small diameter non-peptidergic neurons. The functional significance of alpha7 integrin expression following injury was addressed using dissociated adult rat and mouse sensory neurons. By using function-blocking antibodies and neurons isolated from alpha7 integrin null mice, we demonstrate that NGF- and NT-3-stimulated neurite outgrowth is reduced in the absence of alpha7 integrin signaling. In contrast, GDNF-stimulated neurite outgrowth is less dependent on alpha7 integrin. These results define an essential interaction between alpha7 integrin and laminin for mediating neurite outgrowth of subpopulations of injured adult sensory neurons.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, CD / genetics
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Antigens, CD / metabolism*
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Calcitonin Gene-Related Peptide / metabolism
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Cell Differentiation / drug effects
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Cell Differentiation / physiology
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Cell Size
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Cells, Cultured
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Denervation
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Female
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Ganglia, Spinal / cytology
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Ganglia, Spinal / metabolism*
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Growth Cones / drug effects
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Growth Cones / metabolism
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Growth Cones / ultrastructure
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Integrin alpha Chains / genetics
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Integrin alpha Chains / metabolism*
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Laminin / metabolism
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Male
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Mice
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Mice, Knockout
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Nerve Growth Factors / metabolism
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Nerve Growth Factors / pharmacology
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Nerve Regeneration / physiology*
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Neurites / drug effects
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Neurites / metabolism*
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Neurites / ultrastructure
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Neurofilament Proteins / metabolism
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Neurons, Afferent / cytology
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Neurons, Afferent / drug effects
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Neurons, Afferent / metabolism*
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Rats
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Rats, Wistar
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Sciatic Nerve / injuries
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Sciatic Nerve / metabolism
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Sciatic Nerve / surgery
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Sciatic Neuropathy / metabolism
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Sciatic Neuropathy / physiopathology
Substances
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Antigens, CD
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Integrin alpha Chains
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Laminin
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Nerve Growth Factors
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Neurofilament Proteins
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integrin alpha7
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neurofilament protein H
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Calcitonin Gene-Related Peptide