Conditional disruption of β1 integrin in Schwann cells impedes interactions with axons

被引:263
作者
Feltri, ML
Porta, DG
Previtali, SC
Nodari, A
Migliavacca, B
Cassetti, A
Littlewood-Evans, A
Reichardt, LF
Messing, A
Quattrini, A
Mueller, U
Wrabetz, L
机构
[1] Ist Sci San Raffaele, Dept Biol & Technol Res, I-20132 Milan, Italy
[2] Ist Sci San Raffaele, Dept Neurosci, I-20132 Milan, Italy
[3] Friedrich Miescher Inst, CH-4058 Basel, Switzerland
[4] Univ Calif San Francisco, Howard Hughes Med Inst, Dept Physiol, San Francisco, CA 94143 USA
[5] Univ Wisconsin, Waisman Ctr, Madison, WI 53705 USA
[6] Univ Wisconsin, Sch Vet Med, Madison, WI 53705 USA
关键词
axo-glial interactions; Cre/loxP; congenital muscular dystrophy; laminin; peripheral nerve;
D O I
10.1083/jcb.200109021
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
In dystrophic mice, a model of merosin-deficient congenital muscular dystrophy, laminin-2 mutations produce peripheral nerve dysmyelination and render Schwann cells unable to sort bundles of axons. The laminin receptor and the mechanism through which dysmyelination and impaired sorting occur are unknown. We describe mice in which Schwann cell-specific disruption of beta1 integrin, a component of laminin receptors, causes a severe neuropathy with impaired radial sorting of axons. beta1-null Schwann cells populate nerves, proliferate, and survive normally, but do not extend or maintain normal processes around axons. Interestingly, some Schwann cells surpass this problem to form normal myelin, possibly due to the presence of other laminin receptors such as dystroglycan and alpha6beta4 integrin. These data suggest that PI integrin links laminin in the basal lamina to the cytoskeleton in order for Schwann cells to ensheath axons, and alteration of this linkage contributes to the peripheral neuropathy of congenital muscular dystrophy.
引用
收藏
页码:199 / 209
页数:11
相关论文
共 56 条
  • [41] IDENTIFICATION OF A NOVEL MUTANT TRANSCRIPT OF LAMININ ALPHA-2 CHAIN GENE RESPONSIBLE FOR MUSCULAR-DYSTROPHY AND DYSMYELINATION IN DY(2J) MICE
    SUNADA, Y
    BERNIER, SM
    UTANI, A
    YAMADA, Y
    CAMPBELL, KP
    [J]. HUMAN MOLECULAR GENETICS, 1995, 4 (06) : 1055 - 1061
  • [42] Induction of postnatal Schwann cell death by the low-affinity neurotrophin receptor in vitro and after axotomy
    Syroid, DE
    Maycox, PJ
    Soilu-Hänninen, M
    Petratos, S
    Bucci, T
    Burrola, P
    Murray, S
    Cheema, S
    Lee, KF
    Lemke, G
    Kilpatrick, TJ
    [J]. JOURNAL OF NEUROSCIENCE, 2000, 20 (15) : 5741 - 5747
  • [43] Cell death in the Schwann cell lineage and its regulation by neuregulin
    Syroid, DE
    Maycox, PR
    Burrola, PG
    Liu, NL
    Wen, DZ
    Lee, KF
    Lemke, G
    Kilpatrick, TJ
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (17) : 9229 - 9234
  • [44] Expression of Rho-family GTPases (Rac, cdc42, RhoA) and their association with p-21 activated kinase in adult rat peripheral nerve
    Terashima, T
    Yasuda, H
    Terada, M
    Kogawa, S
    Maeda, K
    Haneda, M
    Kashiwagi, A
    Kikkawa, R
    [J]. JOURNAL OF NEUROCHEMISTRY, 2001, 77 (04) : 986 - 992
  • [45] TOMASELLI KJ, 1993, J NEUROSCI, V13, P4880
  • [46] Voiculescu O, 2000, GENESIS, V26, P123, DOI 10.1002/(SICI)1526-968X(200002)26:2<123::AID-GENE7>3.0.CO
  • [47] 2-O
  • [48] WEBSTER HD, 1984, PERIPHERAL NEUROPATH, P329
  • [49] Witt A, 2000, GLIA, V29, P112, DOI 10.1002/(SICI)1098-1136(20000115)29:2<112::AID-GLIA3>3.0.CO
  • [50] 2-Z