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.

Cell adhesion and neurite outgrowth are promoted by neurofascin NF155 and inhibited by NF186.

Neurofascin (NF) is a neural cell adhesion molecule in the L1-family containing six Ig domains and multiple fibronectin type III (FnIII) repeats in its extracellular region. NF has many splicing variants and two of these are exemplars that have different cellular patterns of expression during development. NF186, which is expressed on neurons, contains an unusual mucin-like region and NF155, which is expressed on glia, contains a unique FnIII repeat with an RGD motif.

Plasma membrane targeting of SNAP-25 increases its local concentration and is necessary for SNARE complex formation and regulated exocytosis.

SNAP-25 is an integral protein of the plasma membrane involved in neurotransmission and hormone secretion. The cysteine-rich domain of SNAP-25 is essential for membrane binding and plasma-membrane targeting. However, this domain is not required for SNARE complex formation and fusion of membranes in vitro.

Rab3A and Rab3D control the total granule number and the fraction of granules docked at the plasma membrane in PC12 cells.

Rab proteins are Ras-like GTPases that regulate traffic along the secretory or endocytic pathways. Within the Rab family, Rab3 proteins are expressed at high levels in neurons and endocrine cells where they regulate release of dense core granules and synaptic vesicles. Immunoelectron microscopy shows that Rab3A and Rab3D can coexist on the same granule before and after docking.

Role of the cysteine-rich domain of the t-SNARE component, SYNDET, in membrane binding and subcellular localization.

Wild-type syndet is efficiently recruited at the plasma membrane in transfected AtT-20 cells. A deletion at the cysteine-rich domain abolishes palmitoylation, membrane binding, and plasma membrane distribution of syndet. Syndet, SNAP-25A, and SNAP-25B share four cysteine residues, of which three, Cys2, Cys4, and Cys5, are absolutely conserved in all three homologs.