Two Protein N-Acetylgalactosaminyl Transferases Regulate Synaptic Plasticity by Activity-Dependent Regulation of Integrin Signaling

被引:23
作者
Dani, Neil [1 ,2 ,3 ,4 ]
Zhu, He [1 ,2 ,3 ,4 ]
Broadie, Kendal [1 ,2 ,3 ,4 ]
机构
[1] Vanderbilt Univ, Dept Biol Sci, Nashville, TN 37232 USA
[2] Vanderbilt Univ, Dept Cell & Dev Biol, Nashville, TN 37232 USA
[3] Vanderbilt Univ, Dept Pharmacol, Nashville, TN 37232 USA
[4] Vanderbilt Univ, Vanderbilt Kennedy Ctr Res Human Dev, Nashville, TN 37232 USA
关键词
activity dependent; Drosophila; integrin; neuromuscular junction; O-linked glycosylation; plasticity; DROSOPHILA NEUROMUSCULAR-JUNCTION; LONG-TERM POTENTIATION; EXTRACELLULAR-MATRIX; CELL-ADHESION; UDP-GALNAC; RECEPTOR SUBUNIT; HEPARAN-SULFATE; O-GLYCOSYLATION; NERVOUS-SYSTEM; EXPRESSION;
D O I
10.1523/JNEUROSCI.1484-14.2014
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Using a Drosophila whole-genome transgenic RNAi screen for glycogenes regulating synapse function, we have identified two protein alpha-N-acetylgalactosaminyltransferases (pgant3 and pgant35A) that regulate synaptic O-linked glycosylation (GalNAc alpha 1-O-S/T). Loss of either pgant alone elevates presynaptic/postsynaptic molecular assembly and evoked neurotransmission strength, but synapses appear restored to normal in double mutants. Likewise, activity-dependent facilitation, augmentation, and posttetanic potentiation are all suppressively impaired in pgant mutants. In non-neuronal contexts, pgant function regulates integrin signaling, and we show here that the synaptic Position Specific 2 (alpha PS2) integrin receptor and transmembrane tenascin ligand are both suppressively downregulated in pgant mutants. Channelrhodopsin-driven activity rapidly (<1 min) drives integrin signaling in wild-type synapses but is suppressively abolished in pgant mutants. Optogenetic stimulation in pgant mutants alters presynaptic vesicle trafficking and postsynaptic pocket size during the perturbed integrin signaling underlying synaptic plasticity defects. Critically, acute blockade of integrin signaling acts synergistically with pgant mutants to eliminate all activity-dependent synaptic plasticity.
引用
收藏
页码:13047 / 13065
页数:19
相关论文
共 73 条
[1]  
Bahr BA, 1997, J NEUROSCI, V17, P1320
[2]  
Beumer K, 2002, DEVELOPMENT, V129, P3381
[3]  
Beumer KJ, 1999, DEVELOPMENT, V126, P5833
[4]  
BRAND AH, 1993, DEVELOPMENT, V118, P401
[5]   Extracellular Matrix and Its Receptors in Drosophila Neural Development [J].
Broadie, Kendal ;
Baumgartner, Stefan ;
Prokop, Andreas .
DEVELOPMENTAL NEUROBIOLOGY, 2011, 71 (11) :1102-1130
[6]   RELATED CELL-SURFACE ANTIGENS EXPRESSED WITH POSITIONAL SPECIFICITY IN DROSOPHILA IMAGINAL DISKS [J].
BROWER, DL ;
WILCOX, M ;
PIOVANT, M ;
SMITH, RJ ;
REGER, LA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1984, 81 (23) :7485-7489
[7]   DEPLETION OF VESICLES FROM FROG NEUROMUSCULAR JUNCTIONS BY PROLONGED TETANIC STIMULATION [J].
CECCARELLI, B ;
HURLBUT, WP ;
MAURO, A .
JOURNAL OF CELL BIOLOGY, 1972, 54 (01) :30-+
[8]   β1-integrins are required for hippocampal AMPA receptor-dependent synaptic transmission, synaptic plasticity, and working memory [J].
Chan, CS ;
Weeber, EJ ;
Zong, L ;
Fuchs, E ;
Sweatt, JD ;
Davis, RL .
JOURNAL OF NEUROSCIENCE, 2006, 26 (01) :223-232
[9]   Integrin requirement for hippocampal synaptic plasticity and spatial memory [J].
Chan, CS ;
Weeber, EJ ;
Kurup, S ;
Sweatt, JD ;
Davis, RL .
JOURNAL OF NEUROSCIENCE, 2003, 23 (18) :7107-7116
[10]   ERK8 is a negative regulator of O-GalNAc glycosylation and cell migration [J].
Chia, Joanne ;
Tham, Keit Min ;
Gill, David James ;
Bard-Chapeau, Emilie Anne ;
Bard, Frederic A. .
ELIFE, 2014, 3