PKC-phosphorylation of Liprin-α3 triggers phase separation and controls presynaptic active zone structure

Javier Emperador-Melero, Man Yan Wong, Shan Shan H. Wang, Giovanni de Nola, Hajnalka Nyitrai, Tom Kirchhausen and Pascal S. Kaeser ()
Additional contact information
Javier Emperador-Melero: Department of Neurobiology, Harvard Medical School
Man Yan Wong: Department of Neurobiology, Harvard Medical School
Shan Shan H. Wang: Department of Neurobiology, Harvard Medical School
Giovanni de Nola: Department of Neurobiology, Harvard Medical School
Hajnalka Nyitrai: Department of Neurobiology, Harvard Medical School
Tom Kirchhausen: Departments of Cell Biology and Pediatrics, Harvard Medical School and Program in Cellular and Molecular Medicine, Boston Children’s Hospital
Pascal S. Kaeser: Department of Neurobiology, Harvard Medical School

Nature Communications, 2021, vol. 12, issue 1, 1-17

Abstract: Abstract The active zone of a presynaptic nerve terminal defines sites for neurotransmitter release. Its protein machinery may be organized through liquid–liquid phase separation, a mechanism for the formation of membrane-less subcellular compartments. Here, we show that the active zone protein Liprin-α3 rapidly and reversibly undergoes phase separation in transfected HEK293T cells. Condensate formation is triggered by Liprin-α3 PKC-phosphorylation at serine-760, and RIM and Munc13 are co-recruited into membrane-attached condensates. Phospho-specific antibodies establish phosphorylation of Liprin-α3 serine-760 in transfected cells and mouse brain tissue. In primary hippocampal neurons of newly generated Liprin-α2/α3 double knockout mice, synaptic levels of RIM and Munc13 are reduced and the pool of releasable vesicles is decreased. Re-expression of Liprin-α3 restored these presynaptic defects, while mutating the Liprin-α3 phosphorylation site to abolish phase condensation prevented this rescue. Finally, PKC activation in these neurons acutely increased RIM, Munc13 and neurotransmitter release, which depended on the presence of phosphorylatable Liprin-α3. Our findings indicate that PKC-mediated phosphorylation of Liprin-α3 triggers its phase separation and modulates active zone structure and function.

Date: 2021
References: Add references at CitEc
Citations: View citations in EconPapers (4)

Downloads: (external link)
https://www.nature.com/articles/s41467-021-23116-w Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23116-w

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-23116-w

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().