Domain-specific activation of neuronal migration and neurite outgrowth-promoting activities of laminin.
The ECM glycoprotein laminin has profound and varied actions on neurons in vitro. Little is known about how laminin's multiple domains and receptor-binding sites interact in determining its overall effects. Here, it is shown that laminin's ability to promote migration of olfactory epithelium neuronal cells maps to distal long arm domain E8 and is mediated by alpha 6 beta 1 integrin. Surprisingly, treatment of laminin with antibodies against its short arms (domains E1' or P1') uncovered a new neuronal migration-promoting activity, mediated by a beta 1 integrin other than alpha 6 beta 1. Laminin treated with anti-short arm antibodies also promoted beta 1 integrin-dependent neurite outgrowth from late embryonic retinal neurons, which are normally unresponsive to laminin. These "antibody-induced" migration and neurite outgrowth activities mapped to laminin's distal long arm, far from the site(s) of antibody binding. Evidence is presented that the induced activities are not actually cryptic in laminin, but are suppressed by an activity that is located in laminin's P1' domain and that may be lacking in the laminin homolog merosin.
Calof
A L
AL
Department of Biological Sciences, University of Iowa, Iowa City 52242.
Campanero
M R
MR
O'Rear
J J
JJ
Yurchenco
P D
PD
Lander
A D
AD
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects; D004847:Epithelial Cells; D006801:Humans; D039121:Integrin alpha6beta1; D016023:Integrins / Q000502:physiology; D007797:Laminin / Q000737:chemistry / Q000276:immunology / Q000502:physiology*; D051379:Mice; D016501:Neurites / Q000187:drug effects / Q000502:physiology*; D018034:Olfactory Receptor Neurons / Q000196:embryology / Q000502:physiology* / Q000648:ultrastructure; D012513:Sarcoma, Experimental; D013329:Structure-Activity Relationship
D000906:Antibodies; D039121:Integrin alpha6beta1; D016023:Integrins; D007797:Laminin