 |
||||
|
||||
|
||||
|
||||
Previous Article | Next Article
The Journal of Neuroscience, July 15, 1999, 19(14):5834-5846
Rabphilin Knock-Out Mice Reveal That Rabphilin Is Not Required for Rab3 Function in Regulating Neurotransmitter Release
Oliver M. Schlüter1, 2, Eric Schnell3, Matthijs Verhage2, Thanos Tzonopoulos3, Roger A. Nicoll3, Roger Janz2, Robert C. Malenka3, Martin Geppert1, and Thomas C. Südhof2 1 Abteilung Molekulare Neurobiologie, Max-Planck-Institut für Experimentelle Medizin, 37075 Goettingen, Germany, 2 Center for Basic Neuroscience, Department of Molecular Genetics and Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas 75235, and 3 Departments of Psychiatry, Physiology, and Cellular and Molecular Pharmacology, The University of California, San Francisco, California 94143
Rab3A and rab3C are GTP-binding proteins of synaptic vesicles that regulate vesicle exocytosis. Rabphilin is a candidate rab3 effector at the synapse because it binds to rab3s in a GTP-dependent manner, it is co-localized with rab3s on synaptic vesicles, and it dissociates with rab3s from the vesicles during exocytosis. Rabphilin contains two C2 domains, which could function as Ca2+ sensors in exocytosis and is phosphorylated as a function of stimulation. However, it is unknown what essential function, if any, rabphilin performs. One controversial question regards the respective roles of rab3s and rabphilin in localizing each other to synaptic vesicles: although rabphilin is mislocalized in rab3A knock-out mice, purified synaptic vesicles were shown to require rabphilin for binding of rab3A but not rab3A for binding of rabphilin. To test whether rabphilin is involved in localizing rab3s to synaptic vesicles and to explore the functions of rabphilin in regulating exocytosis, we have now analyzed knock-out mice for rabphilin. Mice that lack rabphilin are viable and fertile without obvious physiological impairments. In rabphilin-deficient mice, rab3A is targeted to synaptic vesicles normally, whereas in rab3A-deficient mice, rabphilin transport to synapses is impaired. These results show that rabphilin binds to vesicles via rab3s, consistent with an effector function of rabphilin for a synaptic rab3-signal. Surprisingly, however, no abnormalities in synaptic transmission or plasticity were observed in rabphilin-deficient mice; synaptic properties that are impaired in rab3A knock-out mice were unchanged in rabphilin knock-out mice. Our data thus demonstrate that rabphilin is endowed with the properties of a rab3 effector but is not essential for the regulatory functions of rab3 in synaptic transmission.
Key words: long-term potentiation; synaptic vesicles; exocytosis; mossy fiber terminals; C2 domain; Ca2+-binding proteins; rab3; synaptotagmin; protein kinase A
Copyright © 1999 Society for Neuroscience 0270-6474/99/19145834-13$05.00/0
This article has been cited by other articles:
P. S. Kaeser, H.-B. Kwon, J. Blundell, V. Chevaleyre, W. Morishita, R. C. Malenka, C. M. Powell, P. E. Castillo, and T. C. Sudhof
RIM1{alpha} phosphorylation at serine-413 by protein kinase A is not required for presynaptic long-term plasticity or learning
PNAS, September 23, 2008; 105(38): 14680 - 14685.
[Abstract] [Full Text] [PDF]
M. A. Gaffield and W. J. Betz
Synaptic Vesicle Mobility in Mouse Motor Nerve Terminals with and without Synapsin
J. Neurosci., December 12, 2007; 27(50): 13691 - 13700.
[Abstract] [Full Text] [PDF]
P. Montaville, C. Schlicker, A. Leonov, M. Zweckstetter, G. M. Sheldrick, and S. Becker
The C2A-C2B Linker Defines the High Affinity Ca2+ Binding Mode of Rabphilin-3A
J. Biol. Chem., February 16, 2007; 282(7): 5015 - 5025.
[Abstract] [Full Text] [PDF]
T. R. Mahoney, Q. Liu, T. Itoh, S. Luo, G. Hadwiger, R. Vincent, Z.-W. Wang, M. Fukuda, and M. L. Nonet
Regulation of Synaptic Transmission by RAB-3 and RAB-27 in Caenorhabditis elegans
Mol. Biol. Cell, June 1, 2006; 17(6): 2617 - 2625.
[Abstract] [Full Text] [PDF]
H.-C. Lu, D. A. Butts, P. S. Kaeser, W.-C. She, R. Janz, and M. C. Crair
Role of efficient neurotransmitter release in barrel map development.
J. Neurosci., March 8, 2006; 26(10): 2692 - 2703.
[Abstract] [Full Text] [PDF]
O. M. Schluter, J. Basu, T. C. Sudhof, and C. Rosenmund
Rab3 Superprimes Synaptic Vesicles for Release: Implications for Short-Term Synaptic Plasticity
J. Neurosci., January 25, 2006; 26(4): 1239 - 1246.
[Abstract] [Full Text] [PDF]
T. Tsuboi and M. Fukuda
The C2B Domain of Rabphilin Directly Interacts with SNAP-25 and Regulates the Docking Step of Dense Core Vesicle Exocytosis in PC12 Cells
J. Biol. Chem., November 25, 2005; 280(47): 39253 - 39259.
[Abstract] [Full Text] [PDF]
G. Baldini, A. M. Martelli, G. Tabellini, C. Horn, K. Machaca, P. Narducci, and G. Baldini
Rabphilin Localizes with the Cell Actin Cytoskeleton and Stimulates Association of Granules with F-actin Cross-linked by {alpha}-Actinin
J. Biol. Chem., October 14, 2005; 280(41): 34974 - 34984.
[Abstract] [Full Text] [PDF]
S. Seino and T. Shibasaki
PKA-Dependent and PKA-Independent Pathways for cAMP-Regulated Exocytosis
Physiol Rev, October 1, 2005; 85(4): 1303 - 1342.
[Abstract] [Full Text] [PDF]
Y.-Y. Huang, S. S. Zakharenko, S. Schoch, P. S. Kaeser, R. Janz, T. C. Sudhof, S. A. Siegelbaum, and E. R. Kandel
Genetic evidence for a protein-kinase-A-mediated presynaptic component in NMDA-receptor-dependent forms of long-term synaptic potentiation
PNAS, June 28, 2005; 102(26): 9365 - 9370.
[Abstract] [Full Text] [PDF]
S. Giovedi, F. Darchen, F. Valtorta, P. Greengard, and F. Benfenati
Synapsin Is a Novel Rab3 Effector Protein on Small Synaptic Vesicles: II. FUNCTIONAL EFFECTS OF THE Rab3A-SYNAPSIN I INTERACTION
J. Biol. Chem., October 15, 2004; 279(42): 43769 - 43779.
[Abstract] [Full Text] [PDF]
S. Chandra, F. Fornai, H.-B. Kwon, U. Yazdani, D. Atasoy, X. Liu, R. E. Hammer, G. Battaglia, D. C. German, P. E. Castillo, et al.
Double-knockout mice for {alpha}- and {beta}-synucleins: Effect on synaptic functions
PNAS, October 12, 2004; 101(41): 14966 - 14971.
[Abstract] [Full Text] [PDF]
O. M. Schluter, F. Schmitz, R. Jahn, C. Rosenmund, and T. C. Sudhof
A Complete Genetic Analysis of Neuronal Rab3 Function
J. Neurosci., July 21, 2004; 24(29): 6629 - 6637.
[Abstract] [Full Text] [PDF]
M. Matsumoto, T. Miki, T. Shibasaki, M. Kawaguchi, H. Shinozaki, J. Nio, A. Saraya, H. Koseki, M. Miyazaki, T. Iwanaga, et al.
Noc2 is essential in normal regulation of exocytosis in endocrine and exocrine cells
PNAS, June 1, 2004; 101(22): 8313 - 8318.
[Abstract] [Full Text] [PDF]
M. Fukuda, E. Kanno, and A. Yamamoto
Rabphilin and Noc2 Are Recruited to Dense-core Vesicles through Specific Interaction with Rab27A in PC12 Cells
J. Biol. Chem., March 26, 2004; 279(13): 13065 - 13075.
[Abstract] [Full Text] [PDF]
M. Fukuda
Distinct Rab Binding Specificity of Rim1, Rim2, Rabphilin, and Noc2. IDENTIFICATION OF A CRITICAL DETERMINANT OF Rab3A/Rab27A RECOGNITION BY Rim2
J. Biol. Chem., April 18, 2003; 278(17): 15373 - 15380.
[Abstract] [Full Text] [PDF]
R. D. Burgoyne and A. Morgan
Secretory Granule Exocytosis
Physiol Rev, April 1, 2003; 83(2): 581 - 632.
[Abstract] [Full Text] [PDF]
O. M. Schluter, M. Khvotchev, R. Jahn, and T. C. Sudhof
Localization Versus Function of Rab3 Proteins. EVIDENCE FOR A COMMON REGULATORY ROLE IN CONTROLLING FUSION
J. Biol. Chem., October 18, 2002; 277(43): 40919 - 40929.
[Abstract] [Full Text] [PDF]
J. Ramalho-Santos, G. Schatten, and R. D. Moreno
Control of Membrane Fusion During Spermiogenesis and the Acrosome Reaction
Biol Reprod, October 1, 2002; 67(4): 1043 - 1051.
[Abstract] [Full Text] [PDF]
D. Riedel, W. Antonin, R. Fernandez-Chacon, G. Alvarez de Toledo, T. Jo, M. Geppert, J. A. Valentijn, K. Valentijn, J. D. Jamieson, T. C. Sudhof, et al.
Rab3D Is Not Required for Exocrine Exocytosis but for Maintenance of Normally Sized Secretory Granules
Mol. Cell. Biol., September 15, 2002; 22(18): 6487 - 6497.
[Abstract] [Full Text] [PDF]
D. J. Strick, D. M. Francescutti, Y. Zhao, and L. A. Elferink
Mammalian Suppressor of Sec4 Modulates the Inhibitory Effect of Rab15 during Early Endocytosis
J. Biol. Chem., August 30, 2002; 277(36): 32722 - 32729.
[Abstract] [Full Text] [PDF]
W. Antonin, M. Wagner, D. Riedel, N. Brose, and R. Jahn
Loss of the Zymogen Granule Protein Syncollin Affects Pancreatic Protein Synthesis and Transport but Not Secretion
Mol. Cell. Biol., March 1, 2002; 22(5): 1545 - 1554.
[Abstract] [Full Text] [PDF]
G. J. O. Evans, M. C. Wilkinson, M. E. Graham, K. M. Turner, L. H. Chamberlain, R. D. Burgoyne, and A. Morgan
Phosphorylation of Cysteine String Protein by Protein Kinase A. IMPLICATIONS FOR THE MODULATION OF EXOCYTOSIS
J. Biol. Chem., December 14, 2001; 276(51): 47877 - 47885.
[Abstract] [Full Text] [PDF]
J. Staunton, B. Ganetzky, and M. L. Nonet
Rabphilin Potentiates Soluble N-Ethylmaleimide Sensitive Factor Attachment Protein Receptor Function Independently of rab3
J. Neurosci., December 1, 2001; 21(23): 9255 - 9264.
[Abstract] [Full Text] [PDF]
A.G. M. Leenders, F. H. L. da Silva, W. E.J.M. Ghijsen, and M. Verhage
Rab3A Is Involved in Transport of Synaptic Vesicles to the Active Zone in Mouse Brain Nerve Terminals
Mol. Biol. Cell, October 1, 2001; 12(10): 3095 - 3102.
[Abstract] [Full Text] [PDF]
L. E. Matesic, R. Yip, A. E. Reuss, D. A. Swing, T. N. O'Sullivan, C. F. Fletcher, N. G. Copeland, and N. A. Jenkins
Mutations in Mlph, encoding a member of the Rab effector family, cause the melanosome transport defects observed in leaden mice
PNAS, August 10, 2001; (2001) 181336698.
[Abstract] [Full Text] [PDF]
D. L. Foletti and R. H. Scheller
Developmental Regulation and Specific Brain Distribution of Phosphorabphilin
J. Neurosci., August 1, 2001; 21(15): 5461 - 5472.
[Abstract] [Full Text] [PDF]
D. L. Foletti, J. T. Blitzer, and R. H. Scheller
Physiological Modulation of Rabphilin Phosphorylation
J. Neurosci., August 1, 2001; 21(15): 5473 - 5483.
[Abstract] [Full Text] [PDF]
T Coppola, H Hirling, V Perret-Menoud, S Gattesco, S Catsicas, G Joberty, I. Macara, and R Regazzi
Rabphilin dissociated from Rab3 promotes endocytosis through interaction with Rabaptin-5
J. Cell Sci., January 5, 2001; 114(9): 1757 - 1764.
[Abstract] [PDF]
O Cremona and P De Camilli
Phosphoinositides in membrane traffic at the synapse
J. Cell Sci., January 3, 2001; 114(6): 1041 - 1052.
[Abstract] [PDF]
Y. Takai, T. Sasaki, and T. Matozaki
Small GTP-Binding Proteins
Physiol Rev, January 1, 2001; 81(1): 153 - 208.
[Abstract] [Full Text] [PDF]
G. L. Reed, M. L. Fitzgerald, and J. Polgar
Molecular mechanisms of platelet exocytosis: insights into the "secrete" life of thrombocytes
Blood, November 15, 2000; 96(10): 3334 - 3342.
[Full Text] [PDF]
L. P. Haynes, G. J. O. Evans, A. Morgan, and R. D. Burgoyne
A Direct Inhibitory Role for the Rab3-specific Effector, Noc2, in Ca2+-regulated Exocytosis in Neuroendocrine Cells
J. Biol. Chem., March 23, 2001; 276(13): 9726 - 9732.
[Abstract] [Full Text] [PDF]
X. Wang, B. Hu, B. Zimmermann, and M. W. Kilimann
Rim1 and Rabphilin-3 Bind Rab3-GTP by Composite Determinants Partially Related through N-terminal alpha -Helix Motifs
J. Biol. Chem., August 24, 2001; 276(35): 32480 - 32488.
[Abstract] [Full Text] [PDF]
Y. Wang, S. Sugita, and T. C. Sudhof
The RIM/NIM Family of Neuronal C2 Domain Proteins. INTERACTIONS WITH Rab3 AND A NEW CLASS OF Src HOMOLOGY 3 DOMAIN PROTEINS
J. Biol. Chem., June 23, 2000; 275(26): 20033 - 20044.
[Abstract] [Full Text] [PDF]
L. E. Matesic, R. Yip, A. E. Reuss, D. A. Swing, T. N. O'Sullivan, C. F. Fletcher, N. G. Copeland, and N. A. Jenkins
Mutations in Mlph, encoding a member of the Rab effector family, cause the melanosome transport defects observed in leaden mice
PNAS, August 28, 2001; 98(18): 10238 - 10243.
[Abstract] [Full Text] [PDF]
|
|
|
|
 |
|