Fam134c and Fam134b shape axonal endoplasmic reticulum architecture in vivo.

Autor:	Iavarone F; Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy. f.iavarone@tigem.it., Zaninello M; Institute for Genetics, Faculty of Mathematics and Natural Sciences, University of Cologne, Cologne, Germany.; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany.; Center for Molecular Medicine, University of Cologne, Cologne, Germany., Perrone M; Department of Experimental Medicine, Division of Pharmacology, University of Campania 'L. Vanvitelli', Naples, Italy., Monaco M; Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy., Barth E; Institute for Genetics, Faculty of Mathematics and Natural Sciences, University of Cologne, Cologne, Germany.; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany., Gaedke F; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany., Pizzo MT; Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy., Di Lorenzo G; Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy., Desiderio V; Department of Experimental Medicine, University of Campania 'Luigi Vanvitelli', Via L. Armanni 5, 80138, Naples, Italy., Sommella E; Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, Fisciano, SA, 84084, Italy., Merciai F; Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, Fisciano, SA, 84084, Italy., Salviati E; Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, Fisciano, SA, 84084, Italy., Campiglia P; Department of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132, Fisciano, SA, 84084, Italy., Luongo L; Department of Experimental Medicine, Division of Pharmacology, University of Campania 'L. Vanvitelli', Naples, Italy., De Leonibus E; Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy. deleonibus@tigem.it.; Institute of Biochemistry and Cell Biology, Monterotondo, Rome, Italy. deleonibus@tigem.it., Rugarli E; Institute for Genetics, Faculty of Mathematics and Natural Sciences, University of Cologne, Cologne, Germany. elena.rugarli@uni-koeln.de.; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany. elena.rugarli@uni-koeln.de.; Center for Molecular Medicine, University of Cologne, Cologne, Germany. elena.rugarli@uni-koeln.de., Settembre C; Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy. settembre@tigem.it.; Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy. settembre@tigem.it.
Jazyk:	angličtina
Zdroj:	EMBO reports [EMBO Rep] 2024 Aug; Vol. 25 (8), pp. 3651-3677. Date of Electronic Publication: 2024 Jul 22.
DOI:	10.1038/s44319-024-00213-7
Abstrakt:	Endoplasmic reticulum (ER) remodeling is vital for cellular organization. ER-phagy, a selective autophagy targeting ER, plays an important role in maintaining ER morphology and function. The FAM134 protein family, including FAM134A, FAM134B, and FAM134C, mediates ER-phagy. While FAM134B mutations are linked to hereditary sensory and autonomic neuropathy in humans, the physiological role of the other FAM134 proteins remains unknown. To address this, we investigate the roles of FAM134 proteins using single and combined knockouts (KOs) in mice. Single KOs in young mice show no major phenotypes; however, combined Fam134b and Fam134c deletion (Fam134b/c dKO ), but not the combination including Fam134a deletion, leads to rapid neuromuscular and somatosensory degeneration, resulting in premature death. Fam134b/c dKO mice show rapid loss of motor and sensory axons in the peripheral nervous system. Long axons from Fam134b/c dKO mice exhibit expanded tubular ER with a transverse ladder-like appearance, whereas no obvious abnormalities are present in cortical ER. Our study unveils the critical roles of FAM134C and FAM134B in the formation of tubular ER network in axons of both motor and sensory neurons. (© 2024. The Author(s).)
Databáze:	MEDLINE
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