Lysophosphatidic acid (LPA) is a serum-derived phospholipid that induces a variety of biological responses in various cells via heterotrimeric G protein-coupled receptors (GPCRsLysophosphatidic acid (LPA) 1 is a serum-derived phospholipid that induces a variety of biological responses in various cells (1)(2)(3)(4)(5). LPA is also the prototypic G protein-coupled receptor (GPCR) ligand that activates MAP kinase, phospholipase C, and small GTPases, etc., via heterotrimeric G proteins (1-5). Three distinct G protein-coupled receptors for LPA have been identified, termed LPA 1 , LPA 2 , and LPA 3 (previously Edg2, Edg4, and Edg7, respectively). LPA signals induce actin rearrangements via the Rho family GTPase, RhoA, Rac1, and Cdc42 (1, 5-6). Rho family GTPases have GDP-bound inactive and GTP-bound active forms, the cycle of which is regulated by Rho guanine nucleotide exchange factors (RhoGEFs) that stimulate the exchange of GDP for GTP (7). Members of the RhoGEF family have a Dbl homology (DH) domain that catalyzes the exchange reaction and a pleckstrin homology (PH) domain immediately C-terminal to the DH domain (8). The PH domain is responsible for both subcellular localization and modulation of DH domain function (8). Recently, it has been recognized that the G 12/13 family mediates signaling from the LPA receptor to RhoA and that RhoGEFs containing regulators of G protein signaling (RGS) domains are involved in these processes (9 -10). RGS domain-containing RhoGEFs have been described p115-RhoGEF, PDZ-RhoGEF, and leukemia-associated RhoGEF (LARG) (11-13). The activation mechanisms of RGS domain-containing RhoGEFs induced by extracellular signals are well known in the case of p115-RhoGEF (14 -15). The RGS domain of p115-RhoGEF stimulates the intrinsic GTPase activity of the G 12 or G 13 ␣ subunit, and activated G 12 or G 13 ␣ subunit binds to the RGS domain of p115-RhoGEF, thereby enhancing its ability to catalyze guanine nucleotide exchange of RhoA. On the other hand, PDZ-RhoGEF and LARG, but not p115-RhoGEF, both have N-terminal PDZ domains. The PDZ domain is known as a modular domain that binds to specific C-terminal peptide sequences of many membrane proteins (16). PDZ domain-containing proteins function as mediators of clustering of neurotransmitter receptors and ion channels, and then are involved in asymmetric distribution of receptors in epithelial cells (17)(18)(19)(20). PDZ-RhoGEF and LARG also bind to the G 12 or G 13 ␣ subunit via RGS domains in a manner similar to p115-RhoGEF, although the molecular mechanisms controlling the GEF activity are not yet fully understood (8,(21)(22)(23). Recently, we and other groups have reported that the PDZ domains of PDZ-RhoGEF and LARG interact directly with the C-terminal domain of Plexin-B1, a Semaphorin-4D (Sema-4D) receptor, and/or the insulin-like growth factor (IGF-1) receptor (24 -29). Stimulation of Sema4D or IGF-I-induced RhoA activation through the complex of Plexin-B1 or IGF-I receptors with PDZ-RhoGEF or LARG. These observations suggest that the PDZ dom...
Semaphorin (also known as collapsin) members are thought to be involved in axon guidance during neural network formation. Here, we report the isolation of a novel member, mouse semaphorin G (M-sema G), which encodes a semaphorin domain followed by a single putative immunoglobulin-like domain, a transmembrane domain, and a cytoplasmic domain. M-sema G is most closely related to M-sema F, which we previously reported, and semB and semC. These four members appear to constitute a transmembrane type subfamily in mouse semaphorins. In contrast to the predominant expression of M-sema F mRNAs in the nervous tissues, M-sema G mRNAs are strongly expressed in lymphoid tissues, especially in the thymus, as well as in the nervous tissues. The mRNAs are also detected in various cell lines from hematopoietic cells. By generating specific antibodies, we confirmed the strong expression of MSema G proteins on the surface of lymphocytes. These results provide the first evidence that semaphorin is expressed on lymphocytes and suggest that semaphorins may play an important role in the immune system, as well as in the nervous system.
The ontogeny of neuropeptides, such as somatostatin (SRIF), substance P (SP), leucine-enkephalin (LE), and neurotensin (NT) in the spinal cord (including the spinal ganglion) of the rat, was examined by means of the indirect immunofluorescence method. SRIF and SP appear in the early fetal period before the establishment of the spinal synaptic transmission system, and their appearance precedes that of LE and NT, thus suggesting that SRIF and SP might have some important role in the development of the spinal cord. Furthermore, a number of SRIF-positive structures are found during the fetal period in the spinal cord; however, SRIF-positive fibers in the ventral horn, lamina V, VI, and X tend to decrease remarkably in number after birth, while those found in the dorsal horn maintain their immunoreactivity even in the adult rats. These facts suggest that SRIF in the latter area might function as a neurotransmitter, whereas in the former areas, SRIF might have another role in the development of the spinal cord. SP-positive structures also made their appearance during the fetal period. SP-positive fibers continue to increase in number after birth, and they can be seen throughout the entire spinal cord even in the adult rats. It becomes difficult to identify SP-positive neurons as the rats grow. Numerous SP-positive cells are demonstrated, however, by colchicine pretreatment, thus suggesting that this system is functioning actively in the adult rats. LE- and NT-positive structures appear at perinatal stages and they continue to increase in number after birth. These facts suggest that these peptides (SP, LE and NT) might act as neurotransmitters.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.