Impeded interaction between Schwann cells and axons in the absence of laminin alpha4.
The Schwann cell basal lamina (BL) is required for normal myelination. Loss or mutations of BL constituents, such as laminin-2 (alpha2beta1gamma1), lead to severe neuropathic diseases affecting peripheral nerves. The function of the second known laminin present in Schwann cell BL, laminin-8 (alpha4beta1gamma1), is so far unknown. Here we show that absence of the laminin alpha4 chain, which distinguishes laminin-8 from laminin-2, leads to a disturbance in radial sorting, impaired myelination, and signs of ataxia and proprioceptive disturbances, whereas the axonal regenerative capacity is not influenced. In vitro studies show poor axon growth of spinal motoneurons on laminin-8, whereas it is extensive on laminin-2. Schwann cells, however, extend longer processes on laminin-8 than on laminin-2, and, in contrast to the interaction with laminin-2, solely use the integrin receptor alpha6beta1 in their interaction with laminin-8. Thus, laminin-2 and laminin-8 have different critical functions in peripheral nerves, mediated by different integrin receptors.
Wallquist
Wilhelm
W
Department of Neuroscience, Karolinska Institute, 171 77 Stockholm, Sweden. wilhelm.wallquist@neuro.ki.se
Plantman
Stefan
S
Thams
Sebastian
S
Thyboll
Jill
J
Kortesmaa
Jarkko
J
Lännergren
Jan
J
Domogatskaya
Anna
A
Ogren
Sven Ove
SO
Risling
Mårten
M
Hammarberg
Henrik
H
Tryggvason
Karl
K
Cullheim
Staffan
S
D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D001522:Behavior, Animal / Q000502:physiology; D002465:Cell Movement / Q000235:genetics; D002478:Cells, Cultured; D002490:Central Nervous System / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D003711:Demyelinating Diseases / Q000235:genetics / Q000473:pathology; D007150:Immunohistochemistry / Q000379:methods; D066298:In Vitro Techniques; D007797:Laminin / Q000172:deficiency* / Q000494:pharmacology / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout / Q000502:physiology; D046529:Microscopy, Electron, Transmission / Q000379:methods; D009128:Muscle Spasticity / Q000235:genetics; D009416:Nerve Regeneration / Q000235:genetics; D009418:S100 Proteins / Q000378:metabolism; D012583:Schwann Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D012584:Sciatic Nerve / Q000254:growth & development / Q000473:pathology / Q000648:ultrastructure; D020426:Sciatic Neuropathy / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
C501370:Lama4 protein, mouse; D007797:Laminin; D009418:S100 Proteins; C110308:laminin 8; C102645:laminin alpha 2