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Journal of Neuroscience, Vol 13, 4880-4888, Copyright © 1993 by Society for Neuroscience
Expression of beta 1 integrins in sensory neurons of the dorsal root ganglion and their functions in neurite outgrowth on two laminin isoforms
KJ Tomaselli, P Doherty, CJ Emmett, CH Damsky, FS Walsh and LF Reichardt
Athena Neurosciences Inc., South San Francisco, California 94080.
Integrins are heterodimeric receptors that mediate responses of neurons and
many other cell types to components of the extracellular matrix. In the
present article, we examine the roles of individual integrin receptors
expressed by spinal sensory neurons of the dorsal root ganglion (DRG) in
mediating interactions with laminin, an extracellular matrix glycoprotein
that promotes neurite outgrowth. DRG neurons were shown to express three
beta 1 integrins that have been shown in other cell types to function as
laminin receptors--high levels of alpha 1 beta 1 and alpha 3 beta 1 and low
levels of alpha 6 beta 1. In addition, DRG neurons were shown to express a
known fibronectin receptor, alpha 5 beta 1, and an integrin with undefined
ligands, alpha 6 beta 4. Function-inhibitory monoclonal antibodies specific
for the alpha 1, alpha 2, alpha 3, alpha 5, and alpha 6 integrin subunits
were used to determine the roles of individual integrins in mediating
neurite outgrowth by DRG neurons on laminin. The results demonstrate that
alpha 1 beta 1 and alpha 3 beta 1 function as laminin receptors on these
neurons. As many as 18 distinct isoforms of laminin may exist, assembled as
heterotrimers containing one each of the different A, B1, or B2 subunit
homologs. In the present study, we characterize neurite outgrowth in
response to two of these isoforms, the AeB1eB2e isoform and the AmB1eB2e
isoform. Results utilizing DRG neurons and a pheochromocytoma cell line
(PC12) indicate that these two isoforms exhibit differential selectivities
for the alpha 1 beta 1 and alpha 3 beta 1 integrins.(ABSTRACT TRUNCATED AT
250 WORDS)
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