INVESTIGADORES
MAYORGA Luis Segundo
artículos
Título:
Sperm from hyh mice carrying a point mutation in aSNAP have a defect in acrosome reaction
Autor/es:
BÁTIZ, LUIS FEDERICO; DE BLAS, G.A.; MICHAUT, M.A.; RAMÍREZ, A.R.; RODRÍGUEZ, F.; RATTO, M.H.; OLIVER, C.; TOMES, C.N.; RODRÍGUEZ, E.M.; MAYORGA, LUIS S.
Revista:
PLoS ONE
Editorial:
Plos
Referencias:
Año: 2009 vol. 4 p. 4963 - 4974
ISSN:
1932-6203
Resumen:
Hydrocephalus with hop gait (hyh) is a
recessive inheritable disease that arose spontaneously in a mouse
strain. A missense mutation in the Napa
gene that results in the substitution of a methionine for isoleucine
at position 105 (M105I) of aSNAP has been detected in
these animals. aSNAP is a
ubiquitous protein that plays a key role in membrane fusion and
exocytosis. In this study, we found that male hyh mice with a mild
phenotype produced morphologically normal and motile sperm, but had a
strongly reduced fertility. When stimulated with progesterone or A23187
(a calcium ionophore), sperm from these animals had a defective
acrosome reaction. It has been reported that the
M105I mutation affects the expression but not the function of the
protein. Consistent with an hypomorphic
phenotype, the testes and epididymides of hyh mice had low amounts of
the mutated protein. In contrast, sperm had aSNAP
levels indistinguishable from those found in wild type cells,
suggesting that the mutated protein is not fully functional for
acrosomal exocytosis. Corroborating this
possibility, addition of recombinant wild type aSNAP
rescued exocytosis in streptolysin O-permeabilized sperm, while the
mutant protein was ineffective. Moreover,
addition of recombinant aSNAP.M105I inhibited
acrosomal exocytosis in permeabilized human and wild type mouse sperm.
We conclude that the M105I mutation affects the expression and also the
function of aSNAP, and that a fully functional aSNAP
is necessary for acrosomal exocytosis, a key event in fertilization