The SAD-1 kinase regulates presynaptic vesicle clustering and axon termination.
During synapse formation, presynaptic axon outgrowth is terminated, presynaptic clusters of vesicles are associated with active zone proteins, and active zones are aligned with postsynaptic neurotransmitter receptors. We report here the identification of a novel serine/threonine kinase, SAD-1, that regulates several aspects of presynaptic differentiation in C. elegans. In sad-1 mutant animals presynaptic vesicle clusters in sensory neurons and motor neurons are diffuse and disorganized. Sensory axons fail to terminate in sad-1 mutants, whereas overexpression of SAD-1 causes sensory axons to terminate prematurely. SAD-1 protein is expressed in the nervous system and localizes to synapse-rich regions of the axons. SAD-1 is related to PAR-1, a kinase that regulates cell polarity during asymmetric cell division. Overexpression of SAD-1 causes mislocalization of vesicle proteins to dendrites, suggesting that sad-1 affects axonal-dendritic polarity as well as synaptic development.
Crump
J G
JG
Departments of Anatomy and of Biochemistry and Biophysics, Howard Hughes Medical Institute, University of California, San Francisco 94143, USA.
Zhen
M
M
Jin
Y
Y
Bargmann
C I
CI
D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D001369:Axons / Q000201:enzymology* / Q000648:ultrastructure; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins; D002628:Chemoreceptor Cells / Q000378:metabolism / Q000648:ultrastructure; D003712:Dendrites / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D009046:Motor Neurons / Q000166:cytology / Q000201:enzymology; D016297:Mutagenesis, Site-Directed; D009469:Neuromuscular Junction / Q000378:metabolism; D017729:Presynaptic Terminals / Q000201:enzymology* / Q000648:ultrastructure; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013572:Synaptic Vesicles / Q000201:enzymology* / Q000648:ultrastructure; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000943:Antigens, Differentiation; D029742:Caenorhabditis elegans Proteins; D047908:Intracellular Signaling Peptides and Proteins; D005680:gamma-Aminobutyric Acid; C409406:PAR-1 protein, C elegans; C421165:sad-1 protein, C elegans; D017346:Protein Serine-Threonine Kinases