Abstract
The receptor tyrosine phosphatase PTPRO is involved in axon guidance, but its intracellular signaling mechanisms are unknown. Signals generated through PTPRO must involve interaction of the intracellular domain with substrates and/or signaling proteins. By screening for proteins interacting with PTPRO's intracellular domain, we have identified a new class of cytoplasmic protein. This novel protein, NPCD (Neuronal Pentraxin with Chromo Domain), has multiple cytoplasmic isoforms generated by alternative splicing that are selectively expressed in neurons. These cytoplasmic NPCD isoforms are composed of a neuronal pentraxin domain (formerly thought exclusively extracellular) linked to a chromo domain (formerly thought exclusively nuclear); this protein motif organization is unprecedented. NPCD isoforms are expressed in numerous regions of the central nervous system, where they are present in distinct subcellular arrangements in different brain regions. NPCD isoforms are mainly associated with the inner side of the plasma membrane in brain neurons and rat PC12 cells in vitro; they are present in cell bodies, processes, and growth cones. The biochemical complexity and neuronal expression pattern of NPCD, together with its interaction with PTPRO, suggests involvement in multiple neuronal processes.
