title: CaMKIIalpha interacts with multi-PDZ domain protein MUPP1 in spermatozoa and prevents spontaneous acrosomal exocytosis.
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.
authors.affiliation: Karolinska Institute, Department of Neuroscience, Stockholm, Sweden.
authors.forename: Frauke
authors.initials: F
authors.lastname: Ackermann
authors.forename: Nele
authors.initials: N
authors.lastname: Zitranski
authors.forename: Heike
authors.initials: H
authors.lastname: Borth
authors.forename: Thomas
authors.initials: T
authors.lastname: Buech
authors.forename: Thomas
authors.initials: T
authors.lastname: Gudermann
authors.forename: Ingrid
authors.initials: I
authors.lastname: Boekhoff
mesh_terms: D000177:Acrosome / Q000502:physiology*; D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005089:Exocytosis; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D054731:PDZ Domains; D011485:Protein Binding; D021381:Protein Transport; D051381:Rats; D013094:Spermatozoa / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C491750:Mpdz protein, mouse; C491749:Mpdz protein, rat; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2