unc-31
UNCoordinated 31
Knowledge Graph Relationships
Outgoing (12)
Incoming (24)
Evidence (39 claims)
Our results suggest that each of these UNC-31 domains support distinct sequential molecular actions of UNC-31 in vesicular exocytosis, including steps in vesicle tethering and docking that bridge vesicle with plasma membrane, and subsequently priming vesicle by initiating the formation of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) core complex.
This process requires the dense-core vesicle regulator UNC-31/CAPS, as unc-31 null mutations eliminate both the increased mPSC amplitude and elevated ACR-16 expression in cpx-1 mutants.
Similar neuropeptide secretion defects were found in mutants lacking unc-31 (encoding the protein CAPS) or unc-13 (encoding Munc13).
Our results suggest that CAPS/UNC-31 and UNC-13 serve parallel and dedicated roles in dense-core vesicle and synaptic vesicle exocytosis, respectively, in the C. elegans nervous system.
We also demonstrate that UNC-31 is required for UNC-13-mediated augmentation of DCV exocytosis.
Using the auxin-inducible degradation system, we depleted UNC-31 postembryonically from the hermaphrodite nervous system and revealed defects in egg laying, locomotion, and vesicle release that were comparable to those in unc-31 null mutant animals.
Loss of UNC-31 causes multiple phenotypes in C. elegans including reduced motility, retention of late-stage eggs, and reduction in evoked synaptic release.
We find that strong unc-31 mutations cause defects in four functions controlled by the nervous system.
Using the auxin-inducible degradation system, we depleted UNC-31 postembryonically from the hermaphrodite nervous system and revealed defects in egg laying, locomotion, and vesicle release that were comparable to those in unc-31 null mutant animals.
Moreover, disruption of nicotinic acetylcholine receptor subunit acr-16 abolishes the enhanced mPSC amplitude, and the endogenous expression levels of postsynaptic ACR-16 are elevated in cpx-1 mutants.
C. elegans aex-3 mutations cause pleiotropic behavioral defects that are suggestive of reduced synaptic transmission. aex-3 mutations also show strong genetic interactions with mutations in unc-31 and unc-64, two other genes implicated in synaptic transmission.
Thus, DCVs accumulated in unc-31 mutant synapses. bPAC-induced neuropeptide signaling acts presynaptically to enhance vAChT-dependent SV loading with acetylcholine, thus causing increased miniature postsynaptic current amplitudes (mPSCs) and significantly enlarged SVs.
From N- to the C-terminus, UNC-31 contains putative functional domains, including dynactin 1 binding domain (DBD), C2, PH, (M)UNC-13 homology domain (MHD) and DCV binding domain (DCVBD), the last four we examined in this study.
Our results suggest that each of these UNC-31 domains support distinct sequential molecular actions of UNC-31 in vesicular exocytosis, including steps in vesicle tethering and docking that bridge vesicle with plasma membrane, and subsequently priming vesicle by initiating the formation of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) core complex.
Additionally, the synaptic protein UNC-31 [calcium-activated protein for secretion (CAPS)] acts through an inhibitory pathway not explained by previously identified contributions of UNC-31/CAPS to neuropeptide or glutamate transmission.
Similarly, IDA-1, a membrane-associated protein of the DCV, is overexpressed, and its knockdown in epidermis suppresses the organism-wide growth quiescence in response to epidermal ribosome biogenesis inhibition.
Our results suggest that CAPS/UNC-31 and UNC-13 serve parallel and dedicated roles in dense-core vesicle and synaptic vesicle exocytosis, respectively, in the C. elegans nervous system.
Because unc-31 mutants exhibit synaptic transmission defects, we postulated that loss of DCV release in these mutants and the subsequent suppression by tom-1 mutants could simply reflect alterations in synaptic activity, rather than direct regulation of DCV release.
Rescue of unc-13/Munc13 mutant phenotypes by overexpressed open UNC-64/syntaxin suggested a specific function of UNC-13/Munc13 in opening UNC-64/ syntaxin.
We show that this clearance is regulated by neuromodulation as C. elegans mutants in unc-31 and egl-3 have enhanced clearance of P. aeruginosa.