Rab3A and calmodulin regulate acrosomal exocytosis by mechanisms that do not require a direct interaction

Yunes, Roberto; Tomes, Claudia N.; Michaut, Marcela Alejandra; Blas, Gerardo De; Rodríguez, Facundo; Regazzi, Romano; Mayorga, Luis S.

doi:10.1016/s0014-5793(02)03102-2

Cited by 32 publications

(20 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this context, MUPP1 might be involved in passing a Ca 2+ -occupied calmodulin along the acrosomal reaction cascade. It has been suggested that calmodulin controls more than just a single step of the sequential membrane fusion process of the acrosome reaction, ranging from stimulation of Ttype Ca 2+ channels (Bendahmane et al, 2001;Lopez-Gonzalez et al, 2001) to inhibition of the final fusion event (Yunes et al, 2002). This hypothesis of multiple sites of action of calmodulin is extended by the present work demonstrating that the calmodulin antagonist W7 also increases spontaneous acrosomal secretion (Fig.…”

Section: Discussionsupporting

confidence: 76%

CaMKIIα interacts with multi-PDZ domain protein MUPP1 in spermatozoa and prevents spontaneous acrosomal exocytosis

Ackermann

Zitranski

Borth

et al. 2009

Journal of Cell Science

View full text Add to dashboard Cite

show abstract

Section: Discussionsupporting

confidence: 76%

CaMKIIα interacts with multi-PDZ domain protein MUPP1 in spermatozoa and prevents spontaneous acrosomal exocytosis

Ackermann

Zitranski

Borth

et al. 2009

Journal of Cell Science

View full text Add to dashboard Cite

show abstract

“…A calmodulin-mediated effect is possible, since Ca 2+ /calmodulin binds Rab3A [30] and promotes the exchange of GDP for GTP in the Rab3A–GDP dissociation inhibitor complex [31]. Although we have shown that calmodulin has an inhibitory effect on AE in permeabilized sperm and that this effect is not mediated by binding to Rab3A [32], our results do not exclude a role for calmodulin in Rab3A activation. Once Rab3A is activated, cis SNAREs are disassembled by NSF/α-SNAP and become accessible to neurotoxins.…”

Section: Discussionmentioning

confidence: 64%

Dynamics of SNARE Assembly and Disassembly during Sperm Acrosomal Exocytosis

et al. 2005

View full text Add to dashboard Cite

The dynamics of SNARE assembly and disassembly during membrane recognition and fusion is a central issue in intracellular trafficking and regulated secretion. Exocytosis of sperm's single vesicle—the acrosome—is a synchronized, all-or-nothing process that happens only once in the life of the cell and depends on activation of both the GTP-binding protein Rab3 and of neurotoxin-sensitive SNAREs. These characteristics make acrosomal exocytosis a unique mammalian model for the study of the different phases of the membrane fusion cascade. By using a functional assay and immunofluorescence techniques in combination with neurotoxins and a photosensitive Ca2+ chelator we show that, in unactivated sperm, SNAREs are locked in heterotrimeric cis complexes. Upon Ca2+ entry into the cytoplasm, Rab3 is activated and triggers NSF/α-SNAP-dependent disassembly of cis SNARE complexes. Monomeric SNAREs in the plasma membrane and the outer acrosomal membrane are then free to reassemble in loose trans complexes that are resistant to NSF/α-SNAP and differentially sensitive to cleavage by two vesicle-associated membrane protein (VAMP)–specific neurotoxins. Ca2+ must be released from inside the acrosome to trigger the final steps of membrane fusion that require fully assembled trans SNARE complexes and synaptotagmin. Our results indicate that the unidirectional and sequential disassembly and assembly of SNARE complexes drive acrosomal exocytosis.

show abstract

“…First, we made use of the fact that prenylated, GTP␥S-loaded, recombinant Rab3A induces an exocytotic response of a magnitude comparable with that of calcium (29). Pretreatment with the anti-PTP1B antibody or PTP1B D181A inhibited Rab3A-triggered AR by Ͼ90% (Fig.…”

Section: Ptp1b Is Required For Exocytosis In a Human Sperm Armentioning

confidence: 99%

PTP1B Dephosphorylates N-Ethylmaleimide-sensitive Factor and Elicits SNARE Complex Disassembly during Human Sperm Exocytosis

Zarelli

Ruete

Roggero

et al. 2009

Journal of Biological Chemistry

View full text Add to dashboard Cite

The reversible phosphorylation of tyrosyl residues in proteins is a cornerstone of the signaling pathways that regulate numerous cellular responses. Protein tyrosine phosphorylation is controlled through the concerted actions of protein-tyrosine kinases and phosphatases. The goal of the present study was to unveil the mechanisms by which protein tyrosine dephosphorylation modulates secretion. The acrosome reaction, a specialized type of regulated exocytosis undergone by sperm, is initiated by calcium and carried out by a number of players, including tyrosine kinases and phosphatases, and fusion-related proteins such as Rab3A, ␣-SNAP, N-ethylmaleimide-sensitive factor (NSF), SNAREs, complexin, and synaptotagmin VI. We report here that inducers were unable to elicit the acrosome reaction when permeabilized human sperm were loaded with anti-PTP1B antibodies or with the dominant-negative mutant PTP1B D181A; subsequent introduction of wild type PTP1B or NSF rescued exocytosis. Wild type PTP1B, but not PTP1B D181A, caused cis SNARE complex dissociation during the acrosome reaction through a mechanism involving NSF. Unlike its non-phosphorylated counterpart, recombinant phospho-NSF failed to dissociate SNARE complexes from rat brain membranes. These results strengthen our previous observation that NSF activity is regulated rather than constitutive during sperm exocytosis and indicate that NSF must be dephosphorylated by PTP1B to disassemble SNARE complexes. Interestingly, phospho-NSF served as a substrate for PTP1B in an in vitro assay. Our findings demonstrate that phosphorylation of NSF on tyrosine residues prevents its SNARE complex dissociation activity and establish for the first time a role for PTP1B in the modulation of the membrane fusion machinery.

show abstract

Rab3A and calmodulin regulate acrosomal exocytosis by mechanisms that do not require a direct interaction

Cited by 32 publications

References 31 publications

CaMKIIα interacts with multi-PDZ domain protein MUPP1 in spermatozoa and prevents spontaneous acrosomal exocytosis

CaMKIIα interacts with multi-PDZ domain protein MUPP1 in spermatozoa and prevents spontaneous acrosomal exocytosis

Dynamics of SNARE Assembly and Disassembly during Sperm Acrosomal Exocytosis

PTP1B Dephosphorylates N-Ethylmaleimide-sensitive Factor and Elicits SNARE Complex Disassembly during Human Sperm Exocytosis

Contact Info

Product

Resources

About