Identification of Genes That Are Downregulated in the Absence of the POU Domain Transcription Factor pou3f1 (Oct-6, Tst-1, SCIP) in Sciatic Nerve

Abstract

Despite the importance of myelinating Schwann cells in health and disease, little is known about the genetic mechanisms underlying their development. The POU domain transcription factor pou3f1 (Tst-1, SCIP, Oct-6) is required for the normal differentiation of myelinating Schwann cells, but its precise role requires identification of the genes that it regulates. Here we report the isolation of six genes whose expression is reduced in the absence of pou3f1. Only one of these genes, the fatty acid transport protein P2, was known previously to be expressed in Schwann cells. The LIM domain proteins cysteine-rich protein-1 (CRP1) and CRP2 are expressed in sciatic nerve and induced by forskolin in cultured Schwann cells, but only CRP2 requires pou3f1 for normal expression. pou3f1 appears to require the claw paw gene product for activation of at least some of its downstream effector genes. Expression of the novel Schwann cell genes after nerve injury suggests that they are myelin related. One of the genes, tramdorin1, encodes a novel amino acid transport protein that is localized to paranodes and incisures. Our results suggest that pou3f1 functions to activate gene expression in the differentiation of myelinating Schwann cells.

Analysis of congenital hypomyelinating Egr2 Lo/Lo nerves identifies Sox2 as an inhibitor of Schwann cell differentiation and myelination

“…A promyelinating Schwann cell cluster, including SCIP and its putative transcriptional targets, Crp2 and Cxcr4 (17,18), was also found by this analysis. Furthermore, clusters containing genes associated with immature Schwann cells were identified in both the developing (clusters 1 and 2) and injured (cluster 4) nerve data sets.…”

Substrate specificity and transport mode of the proton‐dependent amino acid transporter mPAT2

“…Salts and all other chemicals were obtained from Sigma and Carl Roth AG (Karlsruhe, Germany) of pro analysi quality. L- [3, H]proline (specific activity 60 CiAEmmol )1 ) was purchased from ICN (Irvine, CA, USA). Collagenase A was obtained from Roche Molecular Biochemicals (Mannheim, Germany).…”

“…Whereas substrate affinity is dependent on extracellular pH, proton binding affinity to PAT2 is substrate-independent, favouring a sequential binding of proton followed by substrate. Maximal transport currents are substrate-dependent which suggests that the translocation of the loaded carrier to the internal side is the rate-limiting step.Keywords: electrophysiology; functional characterization; proton symporter; substrate recognition; transport mode.The proton/amino acid transporter family PAT (SLC36) has been identified from human, mouse and rat origin during the last three years [1][2][3][4][5][6][7]. The PAT family is comprised of four members (PAT1-PAT4, SLC36A1-4); the PAT proteins consist of around 470-500 amino acids and are thought to represent integral membrane proteins with a > 60% similarity to each other [8].…”

“…The proton/amino acid transporter family PAT (SLC36) has been identified from human, mouse and rat origin during the last three years [1][2][3][4][5][6][7]. The PAT family is comprised of four members (PAT1-PAT4, SLC36A1-4); the PAT proteins consist of around 470-500 amino acids and are thought to represent integral membrane proteins with a > 60% similarity to each other [8].…”

“…PAT2 could be responsible, along with the high affinity glycine transporters GLYT1 and GLYT2, for the regulation of intracellular and extracellular concentrations of glycine that modulate glycinergic and glutamatergic neurotransmission [14,15]. Moreover, Bermingham et al suggested a role for PAT2 in the differentiation of Schwann cells in rat sciatic nerves [3]. In other tissues than the nervous system, cellular and subcellular expression pattern of the PAT2 protein have not been examined so far, although the mRNA is expressed in various organs such as in lung, kidney, and heart [2,5,7].…”