Expression of beta 1 integrins in sensory neurons of the dorsal root ganglion and their functions in neurite outgrowth on two laminin isoforms.
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)
Tomaselli
K J
KJ
Athena Neurosciences Inc., South San Francisco, California 94080.
Doherty
P
P
Emmett
C J
CJ
Damsky
C H
CH
Walsh
F S
FS
Reichardt
L F
LF
D000818:Animals; D000831:Animals, Newborn; D000906:Antibodies / Q000494:pharmacology; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000502:physiology; D005333:Fetus; D005727:Ganglia, Spinal / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D019012:Integrin beta1; D016023:Integrins / Q000096:biosynthesis* / Q000502:physiology; D007797:Laminin / Q000494:pharmacology*; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000494:pharmacology; D051379:Mice; D016501:Neurites / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D016716:PC12 Cells; D051381:Rats; D017207:Rats, Sprague-Dawley
D000906:Antibodies; D019012:Integrin beta1; D016023:Integrins; D007797:Laminin; D046911:Macromolecular Substances; D008565:Membrane Proteins