title: Impeded interaction between Schwann cells and axons in the absence of laminin alpha4.
abstract: 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.
authors.affiliation: Department of Neuroscience, Karolinska Institute, 171 77 Stockholm, Sweden. wilhelm.wallquist@neuro.ki.se
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Wallquist
authors.forename: Stefan
authors.initials: S
authors.lastname: Plantman
authors.forename: Sebastian
authors.initials: S
authors.lastname: Thams
authors.forename: Jill
authors.initials: J
authors.lastname: Thyboll
authors.forename: Jarkko
authors.initials: J
authors.lastname: Kortesmaa
authors.forename: Jan
authors.initials: J
authors.lastname: Lännergren
authors.forename: Anna
authors.initials: A
authors.lastname: Domogatskaya
authors.forename: Sven Ove
authors.initials: SO
authors.lastname: Ogren
authors.forename: Mårten
authors.initials: M
authors.lastname: Risling
authors.forename: Henrik
authors.initials: H
authors.lastname: Hammarberg
authors.forename: Karl
authors.initials: K
authors.lastname: Tryggvason
authors.forename: Staffan
authors.initials: S
authors.lastname: Cullheim
mesh_terms: 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
chemical_list: C501370:Lama4 protein, mouse; D007797:Laminin; D009418:S100 Proteins; C110308:laminin 8; C102645:laminin alpha 2