Dual role of DENN/MADD (Rab3GEP) in neurotransmission and neuroprotection.
DENN/MADD is a component of a signalling protein complex that is localized to the cytosol and exerts multiple functions by using different binding partners. Human DENN/MADD is physically the same death-domain protein as rat Rab3 GDP/GTP exchange protein (Rab3GEP). DENN/MADD regulates the recycling of Rab3 small G proteins under normal conditions and has an essential role in Ca(2+)-dependent neurotransmitter release and exocytosis. It is also involved in blocking the apoptosis of neuronal cells under conditions of cytotoxic stress. Recent research supports an important role for DENN/MADD in neuroprotection: reduced endogenous DENN/MADD expression and enhanced pro-apoptotic signalling has been found in brains affected by Alzheimer's disease.
Department of Molecular Biology, Osaka Medical Centre for Cancer and Cardiovascular Diseases, Osaka 537-8511, Japan. miyosi-ju@mc.pref.osaka.jp
Jun
J
Miyoshi
Yoshimi
Y
Takai
D000818:Animals; D017209:Apoptosis; D053418:Death Domain Receptor Signaling Adaptor Proteins; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008958:Models, Molecular; D009474:Neurons / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism; D015398:Signal Transduction; D020692:rab3 GTP-Binding Proteins / Q000378:metabolism / Q000502:physiology*
D053418:Death Domain Receptor Signaling Adaptor Proteins; D020662:Guanine Nucleotide Exchange Factors; C105852:MADD protein, human; D047888:Receptors, Tumor Necrosis Factor, Type I; D020692:rab3 GTP-Binding Proteins