Regulation of synapse density by Pumilio RNA-binding proteins
Year: 2024
Type: article
Abstract: The formation, stabilization, and elimination of synapses are tightly regulated during neural development and into adulthood. Pumilio RNA-binding proteins regulate the translation and localization of many synaptic mRNAs and are developmentally downregulated in the brain. We found that simultaneous downregulation of Pumilio 1 and 2 increases both excitatory and inhibitory synapse density in primary hippocampal neurons and promotes synapse maturation. Loss of Pum1 and Pum2 in the mouse brain was associated with an increase in mRNAs involved in mitochondrial function and synaptic translation. These findings reveal a role for developmental Pumilio downregulation as a permissive step in the maturation of synapses and suggest that modulation of Pumilio levels is a cell-intrinsic mechanism by which neurons tune their capacity for synapse stabilization.
Source: Cell Reports
Authors: Lisa K. Randolph, Michaela M. Pauers, José C. Martínez, Leslie J. Sibener, Michael A. Zrzavy, Nyle A. Sharif, Tatiana M. Gonzalez, Kapil V. Ramachandran, Daniel Dominguez, Ulrich Hengst
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,460
Awards: G1240450420, Molecular determinants of neuronal protein homeostasis through plasma membrane-localized proteasome complexes., Post-transcriptional regulation of Snap25 by Pumilio proteins in synaptogenesis, Role of regulated mRNA degradation in the control of axonal mRNA localization and translation., UNC Oncology K12, G4720334866, G5197149029, G769052352, G9000018070, G9000160414, G9000192336, UNC Integrated Translational Oncology Program (UNC-iTOP), UNC Immunotherapy Training Grant (IM-TAG)
OpenAlex ID: W4402617543