Expression of PTPRO during mouse development suggests involvement in axonogenesis and differentiation of NT‐3 and NGF‐dependent neurons

Abstract

Competition and cooperation between type II and type III receptor protein tyrosine phosphatases (RPTPs) regulate axon extension and pathfinding in Drosophila. The first step to investigate whether RPTPs influence axon growth in the more complex vertebrate nervous system is to identify which neurons express a particular RPTP. We studied the expression of mouse PTPRO, a type III RPTP with an extracellular region containing eight fibronectin type III domains, during embryogenesis and after birth. Mouse PTPRO mRNA is expressed exclusively in two cell types: neurons and kidney podocytes. Maximal expression in the brain was coincident with mid to late gestation and axonogenesis in the brain. We cloned two cDNAs, including a splice variant without sequence coding of 28 amino acids within the juxtamembrane domain that was found mostly in kidney. In situ hybridization detected mPTPRO mRNA in the cerebral cortex, olfactory bulb and nucleus, hippocampus, motor neurons, and the spinal cord midline. In addition, mPTPRO mRNA was found throughout dorsal root, cranial, and sympathetic ganglia and within kidney glomeruli. Mouse PTPRO mRNA was observed in neuron populations expressing TrkA, the high-affinity nerve growth factor receptor, or TrkC, the neurotrophin-3 receptor, and immunoreactive mPTPRO and TrkC colocalized in large dorsal root ganglia proprioceptive neurons. Our results suggest that mPTPRO is involved in the differentiation and axonogenesis of central and peripheral nervous system neurons, where it is in a position to modulate intracellular responses to neurotrophin-3 and/or nerve growth factor.

Receptor Tyrosine Phosphatases Guide Vertebrate Motor Axons during Development

“…PTP-␦, PTP-, and LAR bind to the liprin protein family, which is implicated in several aspects of synapse formation (Serra-Pages et al, 1995;Zhen and Jin, 1999;Kaufmann et al, 2002;Wyszynski et al, 2002). Substrates for PTPRO may include Trk receptors (Beltran et al, 2003), in addition to the novel neural protein NPCD (neuronal pentraxin with chromo domain) (Chen and Bixby, 2005a,b). More progress has been made in the discovery of potential substrates for LAR; it can act together with Abl to coordinate phosphorylation/dephosphorylation of the profilin-interacting protein Ena.…”

“…We therefore chose to examine regulation of motor axon growth in the chick lumbosacral spinal cord. Two type IIa RPTPs, PTP-␦ and PTP-, and one type III RPTP, PTPRO, are expressed during the period of axon outgrowth in motor columns of the rodent spinal cord and the chick brachial spinal cord (Yan et al, 1993;Sommer et al, 1997;Chilton and Stoker, 2000;Beltran et al, 2003;Thompson et al, 2003). To determine whether these RPTPs are also expressed in chick lumbosacral motor neurons, we performed in situ hybridization using digoxygenin-labeled riboprobes.…”

Substrate Specificity of R3 Receptor-like Protein-tyrosine Phosphatase Subfamily toward Receptor Protein-tyrosine Kinases

“…Here, the combinations of R3 RPTPs and substrate RPTKs are important in vivo, because a RPTP dephosphorylates a substrate RPTK only when they are expressed in the same cell. Ptpro is preferentially expressed in the nervous system and kidney (22), and expression of Ptprb is restricted to endothelial cells (23). Ptprj is broadly expressed in various cell types, including endothelial, epithelial, hematopoietic, and neuronal cells (24).…”

Microarrays as toxin sensors

“…A number of other genes including those of the cytochrome P450 family exhibited expression changes, not surprising in the light of their role in xenobiotic metabolism. The study also identified a number of novel genes including a protein tyrosine phosphatase, which is thought to play a role in cell growth and differentiation, 13 and is presumably induced in response to CCl 4 -induced liver injury. The data correlate nicely with independent approaches, and extend those observations by affording new information.…”