FGFR-1 signaling is involved in spermiogenesis and sperm capacitation

Cotton, Leanne M.; Gibbs, Gerard M.; Sanchez-Partida, L. G.; Morrison, John R.; Kretser, David Morritz de; O'Bryan, Moira K

doi:10.1242/jcs.02704

Cited by 70 publications

(50 citation statements)

References 69 publications

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“…To corroborate our data with the FGFR inhibitor, we analyzed sec8 phosphorylation in 3T3 fibroblasts cotransfected with NCAM140 and dominant-negative DN-FGFR1 lacking the intracellular kinase domain (Cotton et al, 2006) but containing the extracellular portion of the FGFR1 receptor, which bears the NCAM binding site (Kiselyov et al, 2003). While phosphorylation of sec8 was strongly enhanced in fibroblasts transfected with NCAM140 only (Fig.…”

Section: Ncam Regulates Phosphorylation Of the Exocyst Complexsupporting

confidence: 64%

The Neural Cell Adhesion Molecule Promotes FGFR-Dependent Phosphorylation and Membrane Targeting of the Exocyst Complex to Induce Exocytosis in Growth Cones

Chernyshova

Leshchyns’ka²,

Hsu³

et al. 2011

J. Neurosci.

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The exocyst complex is an essential regulator of polarized exocytosis involved in morphogenesis of neurons. We show that this complex binds to the intracellular domain of the neural cell adhesion molecule (NCAM). NCAM promotes FGF receptor-mediated phosphorylation of two tyrosine residues in the sec8 subunit of the exocyst complex and is required for efficient recruitment of the exocyst complex to growth cones. NCAM at the surface of growth cones induces Ca 2ϩ -dependent vesicle exocytosis, which is blocked by an inhibitor of L-type voltage-dependent Ca 2ϩ channels and tetanus toxin. Preferential exocytosis in growth cones underlying neurite outgrowth is inhibited in NCAM-deficient neurons as well as in neurons transfected with phosphorylation-deficient sec8 and dominant-negative peptides derived from the intracellular domain of NCAM. Thus, we reveal a novel role for a cell adhesion molecule in that it regulates addition of the new membrane to the cell surface of growth cones in developing neurons.

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Section: Ncam Regulates Phosphorylation Of the Exocyst Complexsupporting

confidence: 64%

The Neural Cell Adhesion Molecule Promotes FGFR-Dependent Phosphorylation and Membrane Targeting of the Exocyst Complex to Induce Exocytosis in Growth Cones

Chernyshova

Leshchyns’ka²,

Hsu³

et al. 2011

J. Neurosci.

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“…Two-hundred sperm cells were assessed for acrosome integrity per treatment. Sperm capacitation status was assessed using global tyrosine phosphorylation Western blotting using the 4G10 (Millipore) antibody, as described previously (56), and the percentage of live:dead sperm was assessed using ethidium labeling (SI Materials and Methods).…”

Section: Methodsmentioning

confidence: 99%

Cysteine-rich secretory protein 4 is an inhibitor of transient receptor potential M8 with a role in establishing sperm function

Gibbs¹,

Orta

Reddy³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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110

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The cysteine-rich secretory proteins (CRISPs) are a group of four proteins in the mouse that are expressed abundantly in the male reproductive tract, and to a lesser extent in other tissues. Analysis of reptile CRISPs and mouse CRISP2 has shown that CRISPs can regulate cellular homeostasis via ion channels. With the exception of the ability of CRISP2 to regulate ryanodine receptors, the in vivo targets of mammalian CRISPs function are unknown. In this study, we have characterized the ion channel regulatory activity of epididymal CRISP4 using electrophysiology, cell assays, and mouse models. Through patch-clamping of testicular sperm, the CRISP4 CRISP domain was shown to inhibit the transient receptor potential (TRP) ion channel TRPM8. These data were confirmed using a stably transfected CHO cell line. TRPM8 is a major cold receptor in the body, but is found in other tissues, including the testis and on the tail and head of mouse and human sperm. Functional assays using sperm from wild-type mice showed that TRPM8 activation significantly reduced the number of sperm undergoing the progesteroneinduced acrosome reaction following capacitation, and that this response was reversed by the coaddition of CRISP4. In accordance, sperm from Crisp4 null mice had a compromised ability to undergo to the progesterone-induced acrosome reaction. Collectively, these data identify CRISP4 as an endogenous regulator of TRPM8 with a role in normal sperm function.cysteine-rich secretory proteins | antigen 5 | pathogenesis-related 1 | epididymal maturation | fertility

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“…Daily sperm production (DSP) was determined using a frozen left testis from WT, SH, and DH mice by a procedure that has been previously described. 24 …”

Section: Fertility Assessmentmentioning

confidence: 99%

Activin C Antagonizes Activin A in Vitro and Overexpression Leads to Pathologies in Vivo

Gold

Jetly

O'Bryan

et al. 2009

The American Journal of Pathology

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Activin A is a potent growth and differentiation factor whose synthesis and bioactivity are tightly regulated. Both follistatin binding and inhibin subunit heterodimerization block access to the activin receptor and/or receptor activation. We postulated that the activin-␤ C subunit provides another mechanism regulating activin bioactivity. To test our hypothesis, we examined the biological effects of activin C and produced mice that overexpress activin-␤ C . Activin C reduced activin A bioactivity in vitro; in LNCaP cells, activin C abrogated both activin A-induced Smad signaling and growth inhibition, and in L␤T2 cells, activin C antagonized activin A-mediated activity of an follicle-stimulating hormone-␤ promoter. Transgenic mice that overexpress activin-␤C exhibited disease in testis, liver, and prostate. Male infertility was caused by both reduced sperm production and impaired sperm motility. The livers of the transgenic mice were enlarged because of an imbalance between hepatocyte proliferation and apoptosis. Transgenic prostates showed evidence of hypertrophy and epithelial cell hyperplasia. Additionally, there was decreased evidence of nuclear Smad-2 localization in the testis, liver, and prostate, indicating that overexpression of activin-␤ C antagonized Smad signaling in vivo. Underlying the significance of these findings, human testis, liver, and prostate cancers expressed increased activin-␤C immunoreactivity. This study provides evidence that activin-␤ C is an antagonist of activin A and supplies an impetus to examine its role in development and disease.

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FGFR-1 signaling is involved in spermiogenesis and sperm capacitation

Cited by 70 publications

References 69 publications

The Neural Cell Adhesion Molecule Promotes FGFR-Dependent Phosphorylation and Membrane Targeting of the Exocyst Complex to Induce Exocytosis in Growth Cones

The Neural Cell Adhesion Molecule Promotes FGFR-Dependent Phosphorylation and Membrane Targeting of the Exocyst Complex to Induce Exocytosis in Growth Cones

Cysteine-rich secretory protein 4 is an inhibitor of transient receptor potential M8 with a role in establishing sperm function

Activin C Antagonizes Activin A in Vitro and Overexpression Leads to Pathologies in Vivo

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