The giant protein AHNAK involved in morphogenesis and laminin substrate adhesion of myelinating Schwann cells.
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.
Centre National de la Recherche Scientifique (CNRS), UMR7101, Laboratoire de Neurobiologie des Signaux Intercellulaires, and Université Pierre et Marie Curie, Université Paris 06, IFR-83, Paris, France.
Claudio
C
Salim
Ysander V
YV
Boxberg
Jeanine
J
Alterio
Sophie
S
Féréol
Fatiha
F
Nothias
D000818:Animals; D000831:Animals, Newborn; D002448:Cell Adhesion; D002452:Cell Count; D002454:Cell Differentiation; D002478:Cells, Cultured; D049030:Dystroglycans / Q000378:metabolism; D020868:Gene Silencing; D007797:Laminin / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009186:Myelin Sheath / Q000502:physiology; D009363:Neoplasm Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering; D051381:Rats; D017208:Rats, Wistar; D017474:Receptors, Laminin / Q000378:metabolism; D012583:Schwann Cells / Q000502:physiology* / Q000648:ultrastructure; D012584:Sciatic Nerve / Q000254:growth & development / Q000502:physiology / Q000648:ultrastructure
C489572:Ahnak protein, mouse; C489573:Ahnak protein, rat; D007797:Laminin; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D017474:Receptors, Laminin; D049030:Dystroglycans