A-Kinase Anchoring Protein 4 (AKAP4) is an ERK1/2 Substrate and a Switch Molecule Between CAMP/PKA and PKC/ERK1/2 in Human Spermatozoa

Overview

Journal Sci Rep

Specialty Science

Date 2016 Dec 1

PMID 27901058

Citations 21

Authors

Liat Rahamim Ben-Navi

Tal Almog

Zhong Yao

Rony Seger

Zvi Naor

Affiliations

Soon will be listed here.

Abstract

Mammalian spermatozoa undergo capacitation and acrosome reaction in order to fertilize the egg. The PKC-ERK1/2 pathway plays an important role in human spermatozoa motility, capacitation and the acrosome reaction. Here we demonstrate that ERK1/2 phosphorylates proAKAP4 on Thr265 in human spermatozoa in vitro and in vivo. Cyclic AMP (cAMP) had no effect on ERK1/2 activity in human spermatozoa, but stimulated the MAPK in mouse pituitary LβT2 gonadotrope cells. cAMP via PKA attenuates PKC-dependent ERK1/2 activation only in the presence of proAKAP4. St-HT31, which disrupts PKA-regulatory subunit II (PKA-RII) binding to AKAP abrogates the inhibitory effect of cAMP in human spermatozoa and in HEK293T cells expressing proAKAP4. In transfected HEK293T cells, PMA relocated proAKAP4, but not proAKAP4-T265A to the Golgi in an ERK1/2-dependnet manner. Similarly, AKAP4 is localized to the spermatozoa principal piece and is relocated to the mid-piece and the postacrosomal region by PMA. Furthermore, using capacitated sperm we found that cAMP reduced PMA-induced ERK1/2 activation and acrosome reaction. Thus, the physiological role of the negative crosstalk between the cAMP/PKA/AKAP4 and the PKC/ERK1/2 pathways is to regulate capacitation and acrosome reaction.

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