Differential expression and functions of neuronal and glial neurofascin isoforms and splice variants during PNS development.
The cell adhesion molecule neurofascin (NF) has a major neuronal isoform (NF186) containing a mucin-like domain followed by a fifth fibronectin type III repeat while these domains are absent from glial NF155. Neuronal NF isoforms lacking one or both of these domains are expressed transiently in embryonic dorsal root ganglia (DRG). These two domains are co-expressed in mature NF186, which peaks in expression prior to birth and then persists almost exclusively at nodes of Ranvier on myelinated axons. In contrast, glial NF155 is only detected postnatally with the onset of myelination. All these forms of NF bound homophilically and to Schwann cells but only the mature NF186 isoform inhibits cell adhesion, and this activity may be important in formation of the node of Ranvier. Schwann cells deficient in NF155 myelinated DRG axons in a delayed manner and they showed significantly decreased clustering of both NF and Caspr in regions where paranodes normally form. The combined results suggest that NF186 is expressed prenatally on DRG neurons and it may modulate their adhesive interactions with Schwann cells, which express NF155 postnatally and require it for development of axon-glial paranodal junctions.
Basak
Sayantani
S
W. M. Keck Center for Collaborative Neuroscience and Dept. of Cell Biology and Neuroscience, Rutgers University, 604 Allison Rd., Piscataway, NJ 08854-8082, USA.
Raju
Karthik
K
Babiarz
Joanne
J
Kane-Goldsmith
Noriko
N
Koticha
Darshan
D
Grumet
Martin
M
D017398:Alternative Splicing; D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D018920:Coculture Techniques; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000502:physiology; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D005727:Ganglia, Spinal / Q000166:cytology / Q000196:embryology / Q000254:growth & development; D006801:Humans; D009186:Myelin Sheath / Q000502:physiology; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D012583:Schwann Cells / Q000166:cytology / Q000378:metabolism
D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal; C105177:Cntnap1 protein, rat; D005353:Fibronectins; D009414:Nerve Growth Factors; C504594:Nfasc protein, rat; D020033:Protein Isoforms; D034741:RNA, Small Interfering