[Frontiers in Bioscience 16, 1315-1330, January 1, 2011]

Role of a-kinase anchoring proteins (AKAPs) in reproduction

Michaela Luconi1, Giulia Cantini1, Elisabetta Baldi2, Gianni Forti1

1Department of Clinical Physiopathology-Centre of Research, Endocrinology Unit, Transfer and High Education: "DENOthe" University of Florence, Italy, 2Andrology Unit, Transfer and High Education: "DENOthe" University of Florence, Italy

TABLE OF CONTENTS

1. Abstract
2. Introductory remarks
3. cAMP/PKA signaling
4. Structure and function of AKAPs 4.1.PKA-binding domain
4.2.Localization sequence
4.3.Ability to form super-molecular complexes with other signaling proteins
5. AKAP regulation
6. AKAP and reproduction
6.1. AKAP role in female reproduction
6.2. AKAP role in oogenesis and fertilization
6.3. AKAP and the male gamete
6.3.1. AKAP3 beyond sperm
6.3.2. AKAP ROLE IN sperm motility
6.3.2.1. Structural and molecular bases of sperm motility
6.3.2.2. AKAP3 and AKAP4
6.3.2.3. AKAP genetic defects and asthenozoospermia
6.3.2.4. AKAP3 / AKAP4 platform and sperm motility
7. Conclusions
8. Referen ces

1. ABSTRACT

Rapid spatio-temporal organized intracellular signaling is a pivotal mechanism for regulation of functions in many cells, in particular in the female and male gametes, in which functional regulation through rapid increases in protein content is not possible since the mechanisms of transcription/translation are somehow frozen due to meiosis block or DNA condensationrespectively. A kinase-anchoring proteins (AKAPs) represent a functional conserved family of signal-organizing scaffolding proteins, which due to the specific subcellular distribution and focally compartmentalized cyclic-AMP-dependent protein kinase (PKA) and other enzymes, assuring the coordination of cAMP-responsive events and their integration with other intracellular signals. This review summarizes the actual knowledge on AKAP structure and functions, taking into particular account the role of different AKAPs in regulating reproductive functions such as gametogenesis. Evidence for sperm specific AKAP isoforms and their initiated signaling cascades in mature sperm and the role of this focally activated super-molecular signaling complex in motility are discussed in details with particular emphasis on putative relations between AKAP structural and functional alterations and defects in sperm motility.