Huntingtin-interacting protein 14, a palmitoyl transferase required for exocytosis and targeting of CSP to synaptic vesicles
Document Type
Article
Abstract
Posttranslational modification through palmitoylation regulates protein localization and function. In this study, we identify a role for the Drosophila melanogaster palmitoyl transferase Huntingtin-interacting protein 14 (HIP14) in neurotransmitter release. hip14 mutants show exocytic defects at low frequency stimulation and a nearly complete loss of synaptic transmission at higher temperature. Interestingly, two exocytic components known to be palmitoylated, cysteine string protein (CSP) and SNAP25, are severely mislocalized at hip14 mutant synapses. Complementary DNA rescue and localization experiments indicate that HIP14 is required solely in the nervous system and is essential for presynaptic function. Biochemical studies indicate that HIP14 palmitoylates CSP and that CSP is not palmitoylated in hip14 mutants. Furthermore, the hip14 exocytic defects can be suppressed by targeting CSP to synaptic vesicles using a chimeric protein approach. Our data indicate that HIP14 controls neurotransmitter release by regulating the trafficking of CSP to synapses.
Medical Subject Headings
Acyltransferases (genetics, metabolism); Adaptor Proteins, Signal Transducing (genetics, metabolism); Animals; Drosophila Proteins (genetics, metabolism); Drosophila melanogaster (metabolism, ultrastructure); Exocytosis (physiology); Ganglia, Invertebrate (metabolism, ultrastructure); Nerve Tissue Proteins (genetics, metabolism); Nervous System (metabolism, ultrastructure); Neuromuscular Junction (metabolism, ultrastructure); Neurotransmitter Agents (metabolism); Protein Processing, Post-Translational (physiology); Protein Transport (genetics); Synaptic Transmission (physiology); Synaptic Vesicles (metabolism, ultrastructure)
Publication Date
12-31-2007
Publication Title
The Journal of cell biology
E-ISSN
1540-8140
Volume
179
Issue
7
First Page
1481
Last Page
96
PubMed ID
18158335
Digital Object Identifier (DOI)
10.1083/jcb.200710061
Recommended Citation
Ohyama, Tomoko; Verstreken, Patrik; Ly, Cindy V.; Rosenmund, Tanja; Rajan, Akhila; Tien, An-Chi; Haueter, Claire; Schulze, Karen L.; and Bellen, Hugo J., "Huntingtin-interacting protein 14, a palmitoyl transferase required for exocytosis and targeting of CSP to synaptic vesicles" (2007). Translational Neuroscience. 1999.
https://scholar.barrowneuro.org/neurobiology/1999