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Excitatory glutamatergic synaptic transmission is critically dependent on maintaining an optimal number of postsynaptic AMPA receptors (AMPARs) at each synapse of a given neuron. Here, we show that presynaptic activity, postsynaptic potential, voltage-gated calcium channels (VGCCs) and UNC-43, the C. elegans homolog of CaMKII, control synaptic strength by regulating motor-driven AMPAR transport. Genetic...
The strength of synaptic communication at central synapses depends on the number of ionotropic glutamate receptors, particularly the class gated by the agonist AMPA (AMPARs). Cornichon proteins, evolutionarily conserved endoplasmic reticulum cargo adaptors, modify the properties of vertebrate AMPARs when coexpressed in heterologous cells. However, the contribution of cornichons to behavior and in vivo...
Mutations in LRRK2 are thus far the most frequent known cause of autosomal dominant and idiopathic Parkinson's disease (PD) with prevalent mutations being found within the GTPase (R1441C/G) and kinase (G2019S) domains. Previous in vitro studies have revealed that R1441C and G2019S mutations are associated with increased kinase activity. To better understand LRRK2-linked PD pathogenesis in vivo, we...
Synaptojanin is a lipid phosphatase required to degrade phosphatidylinositol 4,5 bisphosphate (PIP 2 ) at cell membranes during synaptic vesicle recycling [1, 2]. Synaptojanin mutants in C. elegans are severely uncoordinated and are depleted of synaptic vesicles, possibly because of accumulation of PIP 2 [2]. To identify proteins that act downstream of PIP 2 during endocytosis,...
Kex2/subtilisin-like proteinase activity is required for the production of the adult cuticle in the nematode Caenorhabditis elegans. Deletion of the carboxy termini of four of the bli-4/kpc-4 convertase isoforms results in blistering of the adult cuticle. The blisters vary in severity (expressivity) and are not evident in all individuals (reduced penetrance). We have isolated 13 bli-4/kpc-4 mutants...
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