[en] Post-translational modifications (PTMs) of microtubules (MTs) endow them with specific properties that are essential for key cellular functions, such as axonal transport. Polyglutamylation, a PTM that accumulates in long-lived MTs, has been linked to neurodegeneration in the cerebellum when in excess. While hyperglutamylation of MTs leads to neurodegeneration and disrupts the function of specific neuronal subtypes like Purkinje cells, cortical neurons, and hippocampal excitatory neurons, little is known about its impact on inhibitory interneurons and their functional integration into local networks. In this study, we generated a conditional knockout mouse model to deplete cytosolic carboxypeptidase 1 (Ccp1) in GABAergic neurons, a key MT deglutamylase expressed by hippocampal interneurons. Our findings reveal that the loss of Ccp1 has a profound effect on hippocampal parvalbumin (PV)-expressing interneurons, impairing their MT-dependent transport and reducing their perisomatic inhibition of pyramidal cells (PCs) in the CA2 region of the hippocampus.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Le Bail, Romain; Laboratory of Molecular Regulation of Neurogenesis, GIGA Institute, University of Liège, CHU Sart Tilman, 4000 Liège, Belgium
Lakaye, Bernard ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biochimie et physiologie humaine et pathologique
Janke, Carsten; Institut Curie, Université PSL, CNRS UMR3348, Orsay, France ; Université Paris-Saclay, CNRS UMR3348, Orsay, France
Magiera, Maria M; Institut Curie, Université PSL, CNRS UMR3348, Orsay, France ; Université Paris-Saclay, CNRS UMR3348, Orsay, France
Engel, Dominique ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Pharmacologie
Silva, Carla G; Laboratory of Molecular Regulation of Neurogenesis, GIGA Institute, University of Liège, CHU Sart Tilman, 4000 Liège, Belgium
Nguyen, Laurent ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques ; WELBIO Department, WEL Research Institute, Avenue Pasteur, 6, 1300 Wavre, Belgium
Language :
English
Title :
Ccp1 depletion disrupts network integration of hippocampal parvalbumin interneurons.
FRM - Fondation pour la Recherche Médicale ERC - European Research Council ULiège - University of Liège F.R.S.-FNRS - Fonds de la Recherche Scientifique ANR - Agence Nationale de la Recherche FWB - Fédération Wallonie-Bruxelles
Funding text :
The work performed in the Nguyen laboratory is supported by ULi\u00E8ge (Cr\u00E9dit Classique, Cr\u00E9dit classique de la facult\u00E9 de m\u00E9decine), the F.R.S.-F.N.R.S. (PDR T.0185.20; EOS 0019118F-RG36), the WEL Research Institute (CR-2022A-12), the Fonds L\u00E9on Fredericq, the Fondation Simone et Pierre Clerdent, the Fondation M\u00E9dicale Reine Elisabeth, the ERANET Neuron (STEM-MCD and NeuroTalk), the Win2Wal (ChipOmics; #2010126), and the ERC-Synergy (UNFOLD). The Janke lab is supported by the French National Research Agency (ANR) awards ANR-20-CE13-0011 and the Fondation pour la Recherche M\u00E9dicale (FRM) grant MND202003011485.
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