Identification of extracellular-regulated kinase 1/2 and p38MAPK as regulators of human sperm motili
March 29th, 2008 | by admin |Identification of extracellular-regulated kinase 1/2 and p38MAPK as regulators of human sperm motility and acrosome reaction and as predictors of poor spermatozoa quality.
Mature spermatozoa acquire progressive motility only after ejaculation. Their journey in the female reproductive tract includes also suppression of progressive motility, reactivation, capacitation and hyperactivation of motility (whiplash), the mechanisms of which are obscure. MAPKs are key regulatory enzymes in cell signaling, participating in diverse cellular functions such as growth, differentiation, stress and apoptosis. Here we report that ERK1/2 and p38MAPK are primarily localized to the tail of mature human spermatozoa. Surprisingly, c-Jun N-terminal kinase 1/2 which is thought to be ubiquitously expressed could not be detected in mature human spermatozoa. ERK1/2 stimulation is downstream to protein kinase C (PKC) activation, which is also present in the human sperm tail (PKCbetaI and PKCepsilon). ERK1/2 stimulates and p38 inhibits forward and hyperactivated motility, respectively. Both ERK1/2 and p38MAPK are involved in the acrosome reaction. Using a proteomic approach, we identified ARHGAP6, a RhoGAP, as an ERK substrate in PMA-stimulated human spermatozoa. Inverse correlation was obtained between the relative expression level of ERK1, or the relative activation level of p38 and sperm motility, forward progression motility, sperm morphology and viability. Therefore, increased expression of ERK1 and activated p38 can predict poor human sperm quality.
Almog T, Lazar S, Reiss N, Etkovitz N, Milch E, Rahamim N, Dobkin-Bekman M, Rotem R, Kalina M, Ramon J, Raziel A, Breitbart H, Seger R, Naor Z.
Biochemistry, Tel Aviv University, Tel Aviv.