The melanoma-associated antigen ME491 is expressed strongly during early stages of
progression of the tumor. Hotta et al. (1988) cloned the gene by means of DNA-mediated
gene transfer followed by the screening of a lambda genomic library with human repetitive
Alu sequences as a probe. The cloned DNA, after transcription into mouse L-cells,
generated a protein whose characteristics were indistinguishable in Western blot analysis
from the ME491 antigen expressed by human melanoma cells. The sequence of the cDNA
indicates that the antigen has 237 amino acids (molecular weight 25,475) with 4
transmembrane regions and 3 putative N-glycosylation sites.
NCBI Summary:
The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility. This encoded protein is a cell surface glycoprotein that is known to complex with integrins. It may function as a blood platelet activation marker. Deficiency of this protein is associated with Hermansky-Pudlak syndrome. Also this gene has been associated with tumor progression. The use of alternate polyadenylation sites has been found for this gene.
General function
Receptor
Comment
Cellular localization
Plasma membrane
Comment
Ovarian function
Comment
Cell-Secreted Vesicles in Equine Ovarian Follicular Fluid Contain miRNAs and Proteins: A Possible New Form of Cell Communication Within the Ovarian Follicle. da Silveira JC et al. Proper cell communication within the ovarian follicle is critical for the growth and maturation of a healthy oocyte that can be fertilized and develop into an embryo. Cell communication within the follicle involves many signaling molecules and is affected by maternal age. Recent studies indicate that cell communication can be mediated through secretion and uptake of small membrane-enclosed vesicles. The goals of this study were to (1) identify cell-secreted vesicles (microvesicles and exosomes) containing miRNAs and proteins within ovarian follicular fluid, and (2) determine if miRNA level differs in exosomes isolated from follicular fluid in young compared to old mares. We demonstrate the presence of vesicles resembling microvesicles and exosomes in ovarian follicular fluid using transmission electron microscopy, and CD63-positive and RNA containing vesicles using flow cytometry. Moreover, proteomics analysis reveals that follicular fluid-isolated exosomes contain both known exosomal proteins, and proteins not previously reported in isolated exosomes. MiRNAs were detected in microvesicle and exosomes preparations isolated from follicular fluid by real-time PCR analysis. Uptake of fluorescent-labeled microvesicles by granulosa cells was examined using in vitro and in vivo approaches. MiRNA expression profiling reveals that miRNAs in microvesicle and exosomes preparations isolated from follicular fluid also are present within surrounding granulosa and cumulus cells. These studies revealed that cell communication within the mammalian ovarian follicle may involve transfer of bioactive material by microvesicles and exosomes. Finally, miRNAs present in exosomes from ovarian follicular fluid varied with the age of the mare and a number of different miRNAs were detected in young versus old mare follicular fluid.
Expression regulated by
FSH, LH
Comment
Increased in ovulation array.
Ovarian localization
Oocyte, Granulosa, Follicular Fluid
Comment
Molecular characterization ofexosomes and their microRNA cargo in human follicular fluid: bioinformatic analysis reveals that exosomal microRNAs control pathways involved in follicular maturation. Santonocito M 2014 et al.
OBJECTIVE
To characterize well-represented microRNAs in human follicular fluid (FF) and to ascertain whether they are cargo of FF exosomes and whether they are involved in the regulation of follicle maturation.
DESIGN
FF exosomes were characterized by nanosight, flow cytometry, and exosome-specific surface markers. Expression microRNA profiles from total and exosomal FF were compared with those from plasma of the same women.
SETTING
University laboratory and an IVF center.
PATIENT(S)
Fifteen healthy women who had undergone intracytoplasmic sperm injection.
INTERVENTION(S)
None.
MAIN OUTCOME MEASURE(S)
TaqMan low-density array to investigate the expression profile of 384 microRNAs; DataAssist and geNorm for endogenous control identification; significance analysis of microarrays to identify differentially expressed microRNAs; nanosight, flow-cytometry, and bioanalyzer for exosome characterization; bioinformatic tools for microRNAs target prediction, gene ontology, and pathway analysis.
RESULT(S)
We identified 37 microRNAs upregulated in FF as compared with plasma from the same women. Thirty-two were carried by microvesicles that showed the well-characterized exosomal markers CD63 and CD81. These FF microRNAs are involved in critically important pathways for follicle growth and oocyte maturation. Specifically, nine of them target and negatively regulate mRNAs expressed in the follicular microenvironment encoding inhibitors of follicle maturation and meiosis resumption.
CONCLUSION(S)
This study identified a series of exosomal microRNAs that are highly represented in human FF and are involved in follicular maturation. They could represent noninvasive biomarkers of oocyte quality in assisted reproductive technology.
/////////////////////////
Rapp G, et al reported the characterization of three abundant mRNAs from human
ovarian granulosa cells.
Taft RA, et al 2002 reported the identification of genes encoding mouse oocyte secretory and
transmembrane proteins by a signal sequence trap.
At all stages of follicular
development, oocytes interact with surrounding granulosa cells and promote their
differentiation into the types of cells that support further oocyte growth and
developmental competence. These interactions suggest the existence of an
oocyte-granulosa cell regulatory loop that includes both secreted proteins and cell
surface receptors on both cell types. Factors involved in the regulatory loop will
therefore contain a signal sequence, which can be used to identify them through a
signal sequence trap (SST). A screen of an oocyte SST library identified three
classes of oocyte-expressed sequences: known mouse genes, sequences homologous
to known mammalian genes, and novel sequences of unknown function. Many of the
recovered genes may have roles in the oocyte-granulosa cell regulatory loop. For
several of the known mouse genes, new roles in follicular development are implied
by identification of their expression, for the first time, in the oocyte.
CD63 was found by the SST screen.
Follicle stages
Comment
Phenotypes
Mutations
1 mutations
Species: mouse
Mutation name: None
type: null mutation fertility: fertile Comment: The thrombospondin-1 receptor CD36 is an important mediator of ovarian angiogenesis and folliculogenesis. Osz K 2014 et al.
BACKGROUND
Ovarian angiogenesis is a complex process that is regulated by a balance between pro- and anti-angiogenic factors. Physiological processes within the ovary, such as folliculogenesis, ovulation, and luteal formation are dependent upon adequate vascularization and anything that disrupts normal angiogenic processes may result in ovarian dysfunction, and possibly infertility. The objective of this study was to evaluate the role of the thrombospondin-1 (TSP-1) receptor CD36 in mediating ovarian angiogenesis and regulating ovarian function.
METHODS
The role of CD36 was evaluated in granulosa cells in vitro and ovarian morphology and protein expression were determined in wild type and CD36 null mice.
RESULTS
In vitro, CD36 inhibition increased granulosa cell proliferation and decreased apoptosis. Granulosa cells in which CD36 was knocked down also exhibited an increase in expression of survival and angiogenic proteins. Ovaries from CD36 null mice were hypervascularized, with increased expression of pro-angiogenic vascular endothelial growth factor (VEGF) and its receptor VEGFR-2. Ovaries from CD36 null mice contained an increase in the numbers of pre-ovulatory follicles and decreased numbers of corpora lutea. CD36 null mice also had fewer number of offspring compared to wild type controls.
CONCLUSIONS
The results from this study demonstrate that CD36 is integral to the regulation of ovarian angiogenesis by TSP-1 and the expression of these family members may be useful in the control of ovarian vascular disorders.
/////////////////////////