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UNC-30/PITX coordinates neurotransmitter identity with postsynaptic GABA receptor clustering
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UNC-30/PITX coordinates neurotransmitter identity with postsynaptic GABA receptor clustering
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Journal Article
UNC-30/PITX coordinates neurotransmitter identity with postsynaptic GABA receptor clustering
2024
Overview
Terminal selectors are transcription factors that control neuronal identity by regulating the expression of key effector molecules, such as neurotransmitter (NT) biosynthesis proteins, ion channels and neuropeptides. Whether and how terminal selectors control neuronal connectivity is poorly understood. Here, we report that UNC-30 (PITX2/3), the terminal selector of GABA motor neuron identity in
, is required for NT receptor clustering, a hallmark of postsynaptic differentiation. Animals lacking
or
the short isoform of the MN-secreted synapse organizer
(
), display severe GABA receptor type A (GABA
R) clustering defects in postsynaptic muscle cells. Mechanistically, UNC-30 acts directly to induce and maintain transcription of
and GABA biosynthesis genes (e.g.,
,
). Hence, UNC-30 controls GABA
R clustering on postsynaptic muscle cells and GABA biosynthesis in presynaptic cells, transcriptionally coordinating two critical processes for GABA neurotransmission. Further, we uncover multiple target genes and a dual role for UNC-30 both as an activator and repressor of gene transcription. Our findings on UNC-30 function may contribute to our molecular understanding of human conditions, such as Axenfeld-Rieger syndrome, caused by PITX2 and PITX3 gene mutations.
Publisher
Cold Spring Harbor Laboratory Press,Cold Spring Harbor Laboratory
