α7β1 integrin is a receptor for laminin‐2 on Schwann cells

Chernousov, Michael A.; Kaufman, Stephen J.; Stahl, Richard C.; Rothblum, Katrina; Carey, David J.

doi:10.1002/glia.20536

Cited by 25 publications

(17 citation statements)

References 54 publications

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“…19,50 Several laminin receptors are present in mature SCs, but the b1 subfamily of integrins have been shown to play a key role in nerve regeneration, being necessary for SCs-axons interactions and myelination. [51][52][53][54] Consistent with previous studies on the primary role the b1 subfamily of integrin in axonal sorting, 51,52,54 blocking of b1 integrins did not significantly affect adhesion of neither stem cells nor DRGs, but dramatically reduced neurite outgrowth of DRGs alone on laminin, or of DRG in the presence of dASC without laminin coating. However, this effect was reversed when dASC were seeded on laminin, suggesting that laminin preconditioning of dASC can enhance the neurotrophic effect of dASC and also override b1 mediated effects on neurite outgrowth.…”

supporting

confidence: 82%

Extracellular Matrix Molecules Enhance the Neurotrophic Effect of Schwann Cell-Like Differentiated Adipose-Derived Stem Cells and Increase Cell Survival Under Stress Conditions

Summa

Kalbermatten

Raffoul

et al. 2013

Tissue Engineering Part A

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Since the first reports of induction of adipose-derived stem cells (ASC) into neuronal and glial cell phenotypes, expectations have increased regarding their use in tissue engineering applications for nerve repair. Cell adhesion to extracellular matrix (ECM) is a basic feature of survival, differentiation, and migration of Schwann cells (SC) during nerve regeneration, and fibronectin and laminin are two key molecules of this process. Interaction between ECM and SC-like differentiated ASC (dASC) could potentially improve the neurotrophic potential of the stem cells. We have investigated the effect of ECM molecules on SC-like dASC in terms of proliferation, adhesion, and cell viability. Fibronectin and laminin did not affect the proliferation of dASC when compared with cell adherent tissue culture plastic, but significantly improved viability and cell attachment when dASC were exposed to apoptotic conditions. To assess the influence of the ECM molecules on dASC neurotrophic activity, dASC were seeded onto ECM-coated culture inserts suspended above dorsal root ganglia (DRG) sensory neurons. Neurite outgrowth of DRG neurons was enhanced when dASC were seeded on fibronectin and laminin when compared with controls. When DRG neurons and dASC were in direct contact on the various surfaces there was significantly enhanced neurite outgrowth and coculture with laminin-conditioned dASC produced the longest neurites. Compared with primary SCs, dASC grown on laminin produced similar levels of neurite outgrowth in the culture insert experiments but neurite length was shorter in the direct contact groups. Anti b1 integrin blocking antibody could inhibit baseline and dASC evoked neurite elongation but had no effect on outgrowth mediated by laminin-conditioned dASC. ECM molecules had no effect on the levels of nerve growth factor and brain-derived neurotrophic factor secretion from dASC. The results of the study suggest that ECM molecules can significantly improve the potential of dASC for nerve regeneration.

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supporting

confidence: 82%

Extracellular Matrix Molecules Enhance the Neurotrophic Effect of Schwann Cell-Like Differentiated Adipose-Derived Stem Cells and Increase Cell Survival Under Stress Conditions

Summa

Kalbermatten

Raffoul

et al. 2013

Tissue Engineering Part A

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“…Indeed, as shown in Fig. 5, the subcellular distribution of one of the major laminin receptors of SC, dystroglycan (Chernousov et al, 2007;Scherer and Arroyo, 2002), closely resembles that of AHNAK. Thus, in nonconfluent cultures, both AHNAK, and the transmembrane b-dystroglycan chain are preferentially localized in thin, filopodia-like processes, but less abundant in lamellipodia.…”

Section: Analysis Of Potential Ahnak Function In Sc By Sirna Interfermentioning

confidence: 76%

The giant protein AHNAK involved in morphogenesis and laminin substrate adhesion of myelinating Schwann cells

Salim

Boxberg

Alterio

et al. 2008

Glia

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Within the nervous system, expression of the intriguing giant protein AHNAK had been reported so far only for blood-brain barrier forming vascular endothelium. In a screen for genes upregulated after spinal cord injury, we recently identified ahnak as being highly expressed by non-neuronal cells invading the lesion, delimiting the interior surface of cystic cavities in front of barrier-forming astrocytes. Here, we show for the first time that AHNAK is constitutively expressed in peripheral nervous system, notably by myelinating Schwann cells (SCs), in which we investigated its function. During sciatic nerve development, AHNAK is redistributed from adaxonal toward abaxonal SC compartments in contact with basement membrane. AHNAK labeling on myelinated fibers from adult nerve delineates the so-called "Cajal bands," constituting the residual peripheral SC cytoplasm. Its distribution pattern is complementary to that of periaxin, known to be involved in the myelination process. In vitro, nonconfluent cultured primary SCs seeded on laminin express high levels of AHNAK concentrated in their processes, whereas at confluence, AHNAK is downregulated together with laminin receptor dystroglycan. AHNAK silencing by siRNA interference affects SC morphology and laminin-substrate attachment, as well as expression and distribution of dystroglycan. Thus, our results clearly show the implication of AHNAK in SC adhesion to laminin, probably via targeting of the dystroglycan-associated receptor complex. These findings are of high interest regarding the importance of SC-basal lamina interactions for myelination and myelin maintenance, and open up new perspectives for investigations of the molecular mechanisms underlying demyelinating neuropathies.

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“…It is known that laminin influences cellular behaviour via binding to cell surface receptors such as dystroglycan (Yamada et al, 1996) or integrins (Chernousov et al, 2007;Feltri et al, 2002); by contrast, the mechanisms underlying the observed effects of matrilin 2 are currently poorly understood. Except for matrilin 4, all matrilins mediate cell attachment, but the binding does not lead to the formation of focal contacts and reorganization of the actin cytoskeleton.…”

Section: Effects Of Matrilin 2 On Cell Migration and Axonal Outgrowthmentioning

confidence: 99%

The extracellular-matrix protein matrilin 2 participates in peripheral nerve regeneration

Malin

Sonnenberg-Riethmacher

Guseva

et al. 2009

Journal of Cell Science

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Matrilins are adaptor proteins of the extracellular matrix involved in the formation of both collagen-dependent and collagen-independent filamentous networks. Although their molecular structure and binding partners have been characterized, the functional roles of the four matrilin family members in vivo are still largely unknown. Here, we show that matrilin 2, expressed in pre-myelinating Schwann cells during normal development, profoundly influences the behaviour of glial cells and neurons in vitro. When offered as a uniform substrate, matrilin 2 increased neurite outgrowth of dorsal root ganglia (DRG) neurons and enhanced the migration of both cell line- and embryonic DRG-derived Schwann cells. Vice versa, axonal outgrowth and cell migration were decreased in DRG cultures prepared from matrilin-2-deficient mice compared with wild-type (wt) cultures. In stripe assays, matrilin 2 alone was sufficient to guide axonal growth and, interestingly, axons favoured the combination of matrilin 2 and laminin over laminin alone. In vivo, matrilin 2 was strongly upregulated in injured peripheral nerves of adult wild-type mice and failure of protein upregulation in knockout mice resulted in delayed regrowth of regenerating axons and delayed time-course of functional recovery. Strikingly, the functional recovery 2 months after nerve injury was inferior in matrilin-2-deficient mice compared with wild-type littermates, although motoneuron survival, quality of axonal regeneration, estimated by analyses of axonal diameters and degrees of myelination, and Schwann cell proliferation were not influenced by the mutation. These results show that matrilin 2 is a permissive substrate for axonal growth and cell migration, and that it is required for successful nerve regeneration.

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α7β1 integrin is a receptor for laminin‐2 on Schwann cells

Cited by 25 publications

References 54 publications

Extracellular Matrix Molecules Enhance the Neurotrophic Effect of Schwann Cell-Like Differentiated Adipose-Derived Stem Cells and Increase Cell Survival Under Stress Conditions

Extracellular Matrix Molecules Enhance the Neurotrophic Effect of Schwann Cell-Like Differentiated Adipose-Derived Stem Cells and Increase Cell Survival Under Stress Conditions

The giant protein AHNAK involved in morphogenesis and laminin substrate adhesion of myelinating Schwann cells

The extracellular-matrix protein matrilin 2 participates in peripheral nerve regeneration

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