Article ; Online: CaMKIIalpha interacts with multi-PDZ domain protein MUPP1 in spermatozoa and prevents spontaneous acrosomal exocytosis.
2009 Volume 122, Issue Pt 24, Page(s) 4547–4557
Abstract: The success of acrosomal exocytosis, a complex process with a variety of inter-related steps, relies on the coordinated interaction of participating signaling molecules. Since the acrosome reaction resembles Ca(2+)-regulated exocytosis in neurons, we ... ...
| Abstract | The success of acrosomal exocytosis, a complex process with a variety of inter-related steps, relies on the coordinated interaction of participating signaling molecules. Since the acrosome reaction resembles Ca(2+)-regulated exocytosis in neurons, we investigated whether cognate neuronal binding partners of the multi-PDZ domain protein MUPP1, which recruits molecules that control the initial tethering and/or docking between the acrosomal vesicle and the plasma membrane, are also expressed in spermatozoa, and whether they contribute to the regulation of acrosomal secretion. We observed that CaMKIIalpha colocalizes with MUPP1 in the acrosomal region of epididymal spermatozoa where the kinase selectively binds to a region encompassing PDZ domains 10-11 of MUPP1. Furthermore, we found that pre-treating mouse spermatozoa with a CaMKII inhibitor that directly blocks the catalytic region of the kinase, as well as a competitive displacement of CaMKIIalpha from PDZ domains 10-11, led to a significant increase in spontaneous acrosomal exocytosis. Since Ca(2+)-calmodulin releases CaMKIIalpha from the PDZ scaffolding protein, MUPP1 represents a central signaling platform to dynamically regulate the assembly and disassembly of binding partners pertinent to acrosomal secretion, thereby precisely adjusting an increase in Ca(2+) to synchronized fusion pore formation. |
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| MeSH term(s) | Acrosome/physiology ; Animals ; Calcium-Calmodulin-Dependent Protein Kinase Type 2/genetics ; Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism ; Carrier Proteins/chemistry ; Carrier Proteins/genetics ; Carrier Proteins/metabolism ; Exocytosis ; Male ; Mice ; PDZ Domains ; Protein Binding ; Protein Transport ; Rats ; Spermatozoa/metabolism |
| Chemical Substances | Carrier Proteins ; Mpdz protein, mouse ; Mpdz protein, rat ; Calcium-Calmodulin-Dependent Protein Kinase Type 2 (EC 2.7.11.17) |
| Language | English |
| Publishing date | 2009-12-15 |
| Publishing country | England |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 2993-2 |
| ISSN | 1477-9137 ; 0021-9533 |
| ISSN (online) | 1477-9137 |
| ISSN | 0021-9533 |
| DOI | 10.1242/jcs.058263 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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