Integrin-linked kinase is required for laminin-2–induced oligodendrocyte cell spreading and CNS myelination

Chun, Soo Jin; Rasband, Matthew N.; Sidman, Richard L.; Habib, Amyn A.; Vartanian, Timothy

doi:10.1083/jcb.200304154

Cited by 150 publications

(155 citation statements)

References 43 publications

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“…Our studies in vitro, in cultured oligodendrocyte progenitors, indicate that stathmin is elevated by stimuli favoring migrations (i.e., PDGF and bFGF) (Fig. 1), and its expression is downregulated by differentiative stimuli, such as mitogen withdrawal and growth on a laminin substrate, known to favor membrane spreading and myelin formation (Buttery and ffrench-Constant, 1999;Chun et al, 2003). In vivo, in physiological conditions, stathmin is expressed by migratory precursors labeled by PSA-NCAM (Fig.…”

Section: Discussionmentioning

confidence: 99%

Expression of Stathmin, a Developmentally Controlled Cytoskeleton-Regulating Molecule, in Demyelinating Disorders

Liu

Stadelmann²,

Moscarello³

et al. 2005

J. Neurosci.

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Understanding the biological relevance of reexpression of developmental molecules in pathological conditions is crucial for the development of new therapies. In this study, we report the increased expression of stathmin, a developmentally regulated tubulin-binding protein, in the brains of patients with multiple sclerosis (MS). In physiological conditions, stathmin immunoreactivity was observed in polysialic acid-neural cell adhesion molecule-positive migratory progenitors in the subventricular zone, and its expression progressively decreased as the cells matured into oligodendrocytes (OLs). In MS patients, however, stathmin levels were elevated in 2Ј,3Ј-cyclic nucleotide 3Ј-phosphodiesterase-positive OLs, in 10 of 10 bioptic samples analyzed. Increased levels of stathmin were confirmed by Western blot analysis of normal-appearing white matter samples from MS brains. In addition, using mass spectrometry, stathmin was identified as the main component of a specific myelin protein fraction consistently increased in MS preparations compared with controls.To test the biological relevance of increased stathmin levels, primary OL progenitors were transfected using a myc-tagged stathmin cDNA and were allowed to differentiate. Consistent with a distinct role played by this molecule in cells of the OL lineage at different developmental stages, transient transfection in progenitors favored the bipolar migratory phenotype but did not affect survival. However, sustained stathmin levels in differentiating OLs, because of overexpression, resulted in enhanced apoptotic susceptibility.We conclude that stathmin expression in demyelinating disorders could have a dual role. On one hand, by favoring the migratory phenotype of progenitors, it may promote myelin repair. On the other hand, stathmin in mature OLs may indicate cell stress and possibly affect survival.

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Section: Discussionmentioning

confidence: 99%

Expression of Stathmin, a Developmentally Controlled Cytoskeleton-Regulating Molecule, in Demyelinating Disorders

Liu

Stadelmann²,

Moscarello³

et al. 2005

J. Neurosci.

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“…Normal myelination in the optic nerve, corpus callosum, and spinal cord in the absence of ␤1-integrin Previous studies on ECM function in myelination revealed important regional differences in the requirement for these molecules (Chun et al, 2003). Therefore, we analyzed myelination in the optic nerve, corpus callosum, and spinal cord.…”

Section: Targeted Deletion Of the ␤1-integrin Gene Results In Proteinmentioning

confidence: 99%

“…In support of such a role, oligodendrocytes cultured on laminin-2, an ECM molecule expressed in the developing mammalian CNS Tian et al, 1997;Powell et al, 1998), produce enhanced myelin membranes , whereas mice and humans lacking the laminin ␣2 chain (present in laminin-2) show dysmyelination (Jones et al, 2001;Chun et al, 2003). Antibody-blocking experiments and expression of a ␤1-integrin dominant-negative chimeric integrin, ␤1-DN (Relvas et al, 2001), showed that the oligodendrocyte integrin mediating this process is probably ␣6␤1-integrin, the putative laminin integrin receptor expressed by oligodendrocytes.…”

Section: Introductionmentioning

confidence: 99%

β1-Integrin Signaling Mediates Premyelinating Oligodendrocyte Survival But Is Not Required for CNS Myelination and Remyelination

et al. 2006

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Previous reports, including transplantation experiments using dominant-negative inhibition of ␤1-integrin signaling in oligodendrocyte progenitor cells, suggested that ␤1-integrin signaling is required for myelination. Here, we test this hypothesis using conditional ablation of the ␤1-integrin gene in oligodendroglial cells during the development of the CNS. This approach allowed us to study oligodendroglial ␤1-integrin signaling in the physiological environment of the CNS, circumventing the potential drawbacks of a dominant-negative approach. We found that ␤1-integrin signaling has a much more limited role than previously expected. Although it was involved in stage-specific oligodendrocyte cell survival, ␤1-integrin signaling was not required for axon ensheathment and myelination per se. We also found that, in the spinal cord, remyelination occurred normally in the absence of ␤1-integrin. We conclude that, although ␤1-integrin may still contribute to other aspects of oligodendrocyte biology, it is not essential for myelination and remyelination in the CNS.

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“…Previous work has shown that extracellular matrix components, such as laminin-2, promote extensive membrane extension in oligodendrocytes through integrin interactions (Buttery and ffrenchConstant, 1999;Chun et al, 2003;Colognato et al, 2004). The specific downregulation of a clathrin-independent endocytosis pathway by attachment to the extracellular matrix is interesting in this aspect (del Pozo et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Rho Regulates Membrane Transport in the Endocytic Pathway to Control Plasma Membrane Specialization in Oligodendroglial Cells

Kippert¹,

Trajković²,

Rajendran³

et al. 2007

J. Neurosci.

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Differentiation of oligodendrocytes is associated with dramatic changes in plasma membrane structure, culminating in the formation of myelin membrane sheaths. Previous results have provided evidence that regulation of endocytosis may represent a mechanism to control myelin membrane growth. Immature oligodendrocytes have a high rate of clathrin-independent endocytosis for the transport of membrane to late endosomes/lysosomes (LE/Ls). After maturation and receiving signals from neurons, endocytosis is reduced and transport of membrane from LE/Ls to the plasma membrane is triggered. Here, we show that changes in Rho GTPase activity are responsible for switching between these two modes of membrane transport. Strikingly, Rho inactivation did not only reduce the transport of cargo to LE/L but also increased the dynamics of LE/L vesicles. Furthermore, we provide evidence that Rho inactivation results in the condensation of the plasma membrane in a polarized manner. In summary, our data reveal a novel role of Rho: to regulate the flow of membrane and to promote changes in cell surface structure and polarity in oligodendroglial cells. We suggest that Rho inactivation is required to trigger plasma membrane specialization in oligodendrocytes.

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Integrin-linked kinase is required for laminin-2–induced oligodendrocyte cell spreading and CNS myelination

Cited by 150 publications

References 43 publications

Expression of Stathmin, a Developmentally Controlled Cytoskeleton-Regulating Molecule, in Demyelinating Disorders

Expression of Stathmin, a Developmentally Controlled Cytoskeleton-Regulating Molecule, in Demyelinating Disorders

β1-Integrin Signaling Mediates Premyelinating Oligodendrocyte Survival But Is Not Required for CNS Myelination and Remyelination

Rho Regulates Membrane Transport in the Endocytic Pathway to Control Plasma Membrane Specialization in Oligodendroglial Cells

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