The small G protein ARF1 is involved in the coating of vesicles that bud from the Golgi compartments. Chardin et
al. (1996) characterized a protein with a relative molecular mass of 47 kD, which they named ARNO. ARNO contains a
central Sec7 domain that promotes guanine-nucleotide exchange on ARF1. ARNO also contains an amino-terminal
coiled-coil motif and a carboxy-terminal pleckstrin homology (PH) domain. The PH domain mediates an enhancement of
ARNO exchange activity by negatively charged phospholipid vesicles supplemented with phosphatidylinositol bisphosphate.
NCBI Summary:
Pleckstrin homology, Sec7 and coiled/coil domains 2 (PSCD2) is a member of the PSCD family. Members of this family have identical structural organization that consists of an N-terminal coiled-coil motif, a central Sec7 domain, and a C-terminal pleckstrin homology (PH) domain. The coiled-coil motif is involved in homodimerization, the Sec7 domain contains guanine-nucleotide exchange protein (GEP) activity, and the PH domain interacts with phospholipids and is responsible for association of PSCDs with membranes. Members of this family appear to mediate the regulation of protein sorting and membrane trafficking. PSCD2 exhibits GEP activity in vitro with ARF1, ARF3, and ARF6. PSCD2 protein is 83% homologous to PSCD1.
Desensitization of guanine nucleotide binding protein-coupled receptors is a ubiquitous phenomenon
characterized by declining effector activity upon persistent agonist stimulation. The luteinizing
hormone/choriogonadotropin receptor (LH/CGR) in ovarian follicles exhibits desensitization of
effector adenylyl cyclase activity in response to the mid-cycle surge of LH. Uncoupling of the agonist-activated LH/CGR from the stimulatory G protein (G(s)) is
dependent on GTP and attributable to binding of beta-arrestin present in adenylyl cyclase-rich
follicular membrane fraction to the third intracellular (3i) loop of the receptor.
Mukherjee S, et al 2000 reported that
LH/CGR-dependent desensitization is mimicked by ADP ribosylation factor nucleotide-binding site
opener, a guanine nucleotide exchange factor of the small G proteins ADP ribosylation factors (Arfs)
1 and 6, and blocked by synthetic N-terminal Arf6 peptide, suggesting that the GTP-dependent step of
LH/CGR desensitization is receptor-dependent Arf6 activation. Arf activation by GTP and ADP
ribosylation factor nucelotide-binding site opener promotes the release of docked beta-arrestin from
the membrane, making beta-arrestin available for LH/CGR; Arf6 but not Arf1 peptides block
beta-arrestin release from the membrane. Thus, LH/CGR appears to activate two membrane delimited
signaling cascades via two types of G proteins: heterotrimeric G(s) and small G protein Arf6. Arf6
activation releases docked beta-arrestin necessary for receptor desensitization, providing a feedback
mechanism for receptor self-regulation.
Expression regulated by
Comment
Ovarian localization
Oocyte, Granulosa
Comment
Mukherjee S, et al 2001 reported that desensitization of the Luteinizing
Hormone/Choriogonadotropin Receptor in Ovarian
Follicular Membranes Is Inhibited by Catalytically
Inactive ARNO.
They have investigated the participation of endogenous ADP-ribosylation
factor (ARF) nucleotide-binding site opener (ARNO) in desensitization
of the luteinizing hormone/choriogonadotropin (LH/CG) receptor,
independent of receptor internalization, using a cell-free plasma
membrane model. Results show that ARNO is readily detected in follicular
membranes and that levels of membrane-associated ARNO increase
with follicular maturation. The addition of catalytically inactive E156K
ARNO blocks both the release of beta-arrestin1 from its membrane
docking site, based on Western blot analysis, and development of
LH/CG receptor desensitization. Taken
together, these results suggest that LH/CG receptor promotes
beta-arrestin1 release from its membrane docking site to bind to the 3i
loop of the LH/CG receptor via activation of membrane delimited
endogenous ARNO. As ARNO activation is independent of PI 3-kinase
and Gbetagamma, our results are consistent with a role for PIP(2) in
receptor-stimulated ARNO activation.
Yoon SJ, et al reported the identification of differential gene expression in germinal vesicle vs. metaphase II mouse oocytes by using annealing control primers.
By using a new innovative technology, annealing control primer-polymerase chain reaction (ACP-PCR), we identified genes that are differentially expressed in immature GV vs. in mature MII mouse oocytes. The results of the present study will be valuable in understanding the components of oocyte maturation and provide a basis for studies of human oocyte maturation.
Among the DEGs, we recognized three genes (Pscd2, PKD2, and CSN3) that have been reported to function in the protein kinase D (PKD containing pleckstrin homology domain)COP9 signalosome (CSN) signaling pathway (9 and 10). The differential expression of these three genes in GV and MII oocytes was confirmed by quantitative real-time PCR analysis (Fig. 1C).