Biology subjects

Lopez-Hernandez, T.

Publications and source records attributed to Lopez-Hernandez, T..

3 recordsLinked to original sources

bioRxiv2026

Dynamic Modulation of Neural Cell Identity Maintenance via Lysine Acetyltransferase Type 3 Protein Targeted Degradation

Cell identity acquisition during central nervous system development leads to the establishment of cell-specific transcriptional programs. Once acquired, this identity must be actively maintained, among other molecular mechanisms, by the acetylation of cell-type-specific regulatory regions carried out by the lysine acetyltransferases type 3 (KAT3) proteins CBP and p300. Here, we characterize the rapid transcriptional and physiological consequences of KAT3 elimination in neuronal and glial lineages by means of a KAT3-specific PROTAC degrader, providing strong evidence for their central role as neural identity wardens. Importantly, the restoration of KAT3 proteins in glial cells after cell identity erasure resulted in the recovery of the original transcriptome and physiological functions, probing the dynamic nature of neural cell identities. These findings expand the role of CBP/p300 as identity wardens and challenge our perception of terminal cellular identities as static irrevocable states, opening new avenues for neural identity manipulation with biomedical purposes.

neuroscience↗

bioRxiv2025

Ca2+-phospholipid-dependent regulation of Munc13-1 is essential for post-tetanic potentiation at mossy fiber synapses and supports working memory

Hippocampal mossy fiber (hMF) to CA3 pyramidal cell synapses are thought to support the formation of working memory through presynaptic short-term facilitation (STF) and post-tetanic potentiation (PTP). However, the molecular mechanisms underlying these transient forms of synaptic enhancement remain poorly understood. We show here that Munc13-1-mediated priming of synaptic vesicles (SVs) at active zones controls hMF STF and PTP in response to Ca2+-phospholipid and Ca2+-calmodulin (CaM) signaling. Knock-in mice expressing Munc13-1 variants that are insensitive to Ca2+-phospholipid and Ca2+-CaM signaling exhibit severely impaired STF and PTP at hMF synapses. Moreover, the PTP-induction threshold is strongly increased upon the loss of Ca2+-phospholipid-Munc13-1 signaling. Since these synaptic defects are accompanied by working memory deficits, especially in mice expressing the Ca2+-phospholipid-insensitive Munc13-1 variant, we conclude that Ca2+-dependent regulation of Munc13-1-mediated SV priming co-determines hMF short-term plasticity and working memory formation.

neuroscience↗

bioRxiv2021

Clathrin-independent endocytic retrieval of SV proteins mediated by the clathrin adaptor AP-2 at mammalian central synapses

Neurotransmission is based on the exocytic fusion of synaptic vesicles (SVs) followed by endocytic membrane retrieval and the reformation of SVs. Conflicting models have been proposed regarding the mechanisms of SV endocytosis, most notably clathrin/ AP-2-mediated endocytosis and clathrin-independent ultrafast endocytosis. Partitioning between these pathways has been suggested to be controlled by temperature and stimulus paradigm. We report on the comprehensive survey of six major SV proteins to show that SV endocytosis in hippocampal neurons at physiological temperature occurs independent of clathrin while the endocytic retrieval of a subset of SV proteins including the vesicular transporters for glutamate and GABA depend on sorting by the clathrin adaptor AP-2. Our findings highlight a clathrin-independent role of the clathrin adaptor AP-2 in the endocytic retrieval of select SV cargos from the presynaptic cell surface and suggest a unified model for the endocytosis of SV membranes at mammalian central synapses.

neuroscience↗