Résumé :
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Relatively little is known about the precise molecular mechanisms regulating the differentiation-associated morphological changes during Schwann cell (SC) development and regeneration/remyelination after injury, implying specific interactions with the local environment that ultimately converge on a reorganization of the cytoskeleton. We investigated the role in SC differentiation and function of the giant phosphoprotein AHNAK, which we show for the first time to be expressed at high levels in developing and mature SC. A detailed study of the cellular and subcellular distribution of AHNAK during development of the rat sciatic nerve was performed on the light and electron microscope levels. During the first post-natal month, AHNAK distribution shifts from adaxonal compartments to abaxonal and outer-mesaxonal SC membranes in contact with basement membrane, and ultimately delineates the so-called “Cajal bands”, exhibiting a staining pattern complementary to that of periaxin. Highly expressed in non-confluent cultured primary SC seeded on laminin, AHNAK is downregulated in confluent cells, mainly concentrated around the nucleus. Furthermore, we noted that the SC laminin receptor beta-dystroglycan exhibits a similar distribution pattern as AHNAK on both confluent and non-confluent cultured SC. AHNAK silencing in cultured SC via siRNA transfection was found to affect the morphology and adhesive properties of SC. This is likely related to our observation that ahnak-siRNA transfection leads to a reduction of beta-dystroglycan expression levels, and dislocation of the receptor from the plasma membrane. Taken together, these results strongly suggest a role of AHNAK in SC interaction with laminin, an important component of the basement membrane surrounding myelinating SC. Loss or mutation of basal lamina components (e.g. laminin-2), or of laminin receptors (integrins and dystroglycan), is known to cause severe demyelinating pathologies affecting the sensori-motor system. Elucidating the role of AHNAK in SC may thus contribute to our understanding of SC differentiation, myelin formation, and myelin maintenance.
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