Bonnycastle et al. (1994) isolated a genomic clone for HSPA2 and
found that it has a single open reading frame of 1,917 basepairs that encodes a 639-amino acid protein with a predicted
molecular weight of 70,030 Da. HSPA2 is constitutively expressed in
most tissues, with very high levels in testis and skeletal muscle.
A noncanonical role of NOD-like receptor NLRP14 in PGCLC differentiation and spermatogenesis. Yin Y et al. (2020) NOD-like receptors (NLRs) are traditionally recognized as major inflammasome components. The role of NLRs in germ cell differentiation and reproduction is not known. Here, we identified the gonad-specific Nlrp14 as a pivotal regulator in primordial germ cell-like cell (PGCLC) differentiation in vitro. Physiologically, knock out of Nlrp14 resulted in reproductive failure in both female and male mice. In adult male mice, Nlrp14 knockout (KO) inhibited differentiation of spermatogonial stem cells (SSCs) and meiosis, resulting in trapped SSCs in early stages, severe oligozoospermia, and sperm abnormality. Mechanistically, NLRP14 promoted spermatogenesis by recruiting a chaperone cofactor, BAG2, to bind with HSPA2 and form the NLRP14-HSPA2-BAG2 complex, which strongly inhibited ChIP-mediated HSPA2 polyubiquitination and promoted its nuclear translocation. Finally, loss of HSPA2 protection and BAG2 recruitment by NLRP14 was confirmed in a human nonsense germline variant associated with male sterility. Together, our data highlight a unique proteasome-mediated, noncanonical function of NLRP14 in PGCLC differentiation and spermatogenesis, providing mechanistic insights of gonad-specific NLRs in mammalian germline development.//////////////////
Khanna A et al investigated whether physiological and pharmacological
inhibitors of luteal function would induce HSP-70 in rat luteal cells. Both 35S-methionine labeling and Western blotting
with antibodies against the inducible form of HSP-70 revealed HSP induction in rat luteal cells by prostaglandin
Genes whose expression is detected by cDNA array hybridization: stress response, cell/cell communication Rozenn Dalbis-Tran and Pascal Mermilloda
F2 alpha (PGF2 alpha) coincident with inhibition of progesterone synthesis. In contrast, PGE2 failed to increase
HSP-70 synthesis. Phorbol 12-myristate 13 acetate , tumor necrosis factor-alpha , and ionomycin also induced HSP synthesis.
The finding that a number of factors that inhibit
hormone-sensitive progesterone synthesis rapidly activate the heat shock response implicates HSPs as possible
mediators of luteolysis.
Brevini-Gandolfi TA et al reported that the length of the poly(A) tail of heat shock protein 70 was determined at the germinal vesicle (GV) and metaphase II (MII) stage. The results indicated that the poly(A) tail of this gene is shorter
after in vitro maturation (IVM).
Expression regulated by
Growth Factors/ cytokines
Comment
Kim et al
investigated whether HSP-70 is induced in human granulosa-luteal cells and its relationship to
steroidogenesis. [35S]Methionine labelling showed an increase in a 70 kDa protein after heat treatment which was
demonstrated to be HSP-70 by Western analysis using monoclonal antibodies against the constitutive and inducible forms of
HSP-70. Induction of HSP-70 in human granulosa-luteal cells was also seen with interferon (IFN) gamma, tumour
necrosis factor (TNF)-alpha and a combination of IFN gamma/TNF-alpha . An increase in activated heat shock
factor, which binds to the heat shock transcriptional control element, was detected after heat shock, IFN/TNF, and IFN
treatment. Coincident with the induction of HSP-70 by heat shock was the inhibition of progesterone production compared
with non-shocked granulosa-luteal cells.
Ovarian localization
Oocyte, Granulosa, Luteal cells, Large luteal cells
Comment
Immunofluorescent staining was used by Murdoch WJ to detect in situ alterations in inducible heat shock (stress) protein (HSP)-70 production and DNA fragmentation (indicative of apoptotic cell death) in luteal tissues obtained from sheep after in vivo
administration of a luteolytic dose of PGF2 alpha. Accumulation of HSP-70 was localized to PG-sensitive (i.e., large) luteal
cells. Cytoplasmic HSP-70 increased within 2 h after treatment. Luteal concentrations of progesterone decreased precipitously thereafter. Expression of HSP-70 diminished by 16 h. An increase in immunostained digoxigenin-labeled DNA
was not detected until the onset of structural involution at 16 h; both large and small steroidogenic cells were affected. It was
suggested that HSP-70 induction by PGF2 alpha is a prelude to steroid depletion and active apoptotic death of luteal cells.
Follicle stages
Preovulatory, Corpus luteum
Comment
Phenotypes
Mutations
1 mutations
Species: mouse
Mutation name: None
type: null mutation fertility: fertile Comment:Dix et al. (1996) showed that female homozygous knockout mice for Hsp70-2 undergo normal meiosis and are fertile. In
contrast, homozygous male knockout mice lacked postmeiotic spermatids and mature sperm and were infertile.