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  • Fam134c and Fam134b shape axonal endoplasmic reticulum architecture in vivo.

Fam134c and Fam134b shape axonal endoplasmic reticulum architecture in vivo.

EMBO reports (2024-07-23)
Francescopaolo Iavarone, Marta Zaninello, Michela Perrone, Mariagrazia Monaco, Esther Barth, Felix Gaedke, Maria Teresa Pizzo, Giorgia Di Lorenzo, Vincenzo Desiderio, Eduardo Sommella, Fabrizio Merciai, Emanuela Salviati, Pietro Campiglia, Livio Luongo, Elvira De Leonibus, Elena Rugarli, Carmine Settembre
ABSTRACT

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/cdKO), but not the combination including Fam134a deletion, leads to rapid neuromuscular and somatosensory degeneration, resulting in premature death. Fam134b/cdKO mice show rapid loss of motor and sensory axons in the peripheral nervous system. Long axons from Fam134b/cdKO 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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Monoclonal Anti-Glial Fibrillary Acidic Protein (GFAP) antibody produced in mouse, clone G-A-5, ascites fluid
Sigma-Aldrich
Anti-FAM134C antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
Sigma-Aldrich
Anti-FAM134A antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody
Sigma-Aldrich
Anti-Choline Acetyltransferase Antibody, Chemicon®, from goat
Sigma-Aldrich
Anti-FAM134B antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody
Sigma-Aldrich
Anti-NeuN Antibody, clone A60, clone A60, Chemicon®, from mouse