ANTXR1 deficiency promotes fibroblast senescence: implications for GAPO syndrome as a progeroid disorder.

ANTXR1 is one of two cell surface receptors mediating the uptake of the anthrax toxin into cells. Despite substantial research on its role in anthrax poisoning and a proposed function as a collagen receptor, ANTXR1's physiological functions remain largely undefined. Pathogenic variants in ANTXR1 lead to the rare GAPO syndrome, named for its four primary features: Growth retardation, Alopecia, Pseudoanodontia, and Optic atrophy. The disease is also associated with a complex range of other phenotypes impacting the cardiovascular, skeletal, pulmonary and nervous systems. Aberrant accumulation of extracellular matrix components and fibrosis are considered to be crucial components in the pathogenesis of GAPO syndrome, contributing to the shortened life expectancy of affected individuals. Nonetheless, the specific mechanisms connecting ANTXR1 deficiency to the clinical manifestations of GAPO syndrome are largely unexplored. In this study, we present evidence that ANTXR1 deficiency initiates a senescent phenotype in human fibroblasts, correlating with defects in nuclear architecture and actin dynamics. We provide novel insights into ANTXR1's physiological functions and propose GAPO syndrome to be reconsidered as a progeroid disorder highlighting an unexpected role for an integrin-like extracellular matrix receptor in human aging.

Collagen XXVIII is a distinctive component of the peripheral nervous system nodes of ranvier and surrounds nonmyelinating glial cells.

Growing evidence indicates that collagens perform crucial functions during the development and organization of the nervous system. Collagen XXVIII is a recently discovered collagen almost exclusively expressed in the peripheral nervous system (PNS). In this study, we show that this collagen is associated with nonmyelinated regions of the PNS. With the notable exception of type II terminal Schwann cell in the hairy skin, collagen XXVIII surrounds all nonmyelinating glial cells studied. This includes satellite glial cells of the dorsal root ganglia, terminal Schwann cells type I around mechanoceptors in the skin, terminal Schwann cells around proprioceptors in the muscle spindle or at the neuromuscular junction and olfactory ensheathing cells. Collagen XXVIII is also detected at nodes of Ranvier where the myelin sheath of myelinated fibers is interrupted and is thus a distinctive component of the PNS nodal gap. The correlation between the absence of myelin and the presence of collagen XXVIII is confirmed in a mouse model of Charcot-Marie-Tooth characterized by dysmyelinated nerve fibers, in which enhancement of collagen XXVIII labeling is observed.