Alpha7 integrin mediates neurite outgrowth of distinct populations of adult sensory neurons.
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.
Gardiner
Natalie J
NJ
School of Biological Sciences, University of Manchester, Manchester, M13 9PT, UK.
Fernyhough
Paul
P
Tomlinson
David R
DR
Mayer
Ulrike
U
von der Mark
Helga
H
Streuli
Charles H
CH
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D048429:Cell Size; D002478:Cells, Cultured; D003714:Denervation; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism*; D020439:Growth Cones / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D039001:Integrin alpha Chains / Q000235:genetics / Q000378:metabolism*; D007797:Laminin / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009414:Nerve Growth Factors / Q000378:metabolism / Q000494:pharmacology; D009416:Nerve Regeneration / Q000502:physiology*; D016501:Neurites / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D016900:Neurofilament Proteins / Q000378:metabolism; D009475:Neurons, Afferent / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000293:injuries / Q000378:metabolism / Q000601:surgery; D020426:Sciatic Neuropathy / Q000378:metabolism / Q000503:physiopathology
D015703:Antigens, CD; D039001:Integrin alpha Chains; D007797:Laminin; D009414:Nerve Growth Factors; D016900:Neurofilament Proteins; C085725:integrin alpha7; C051774:neurofilament protein H; D015740:Calcitonin Gene-Related Peptide