Neph1-Robo mechanical anchoring stabilizes neurite branch orientation independently of receptor-specific intracellular signaling
Year: 2026
Type: preprint
Abstract: Neurite morphogenesis is classically viewed as a signal-driven process in which extracellular cues activate intracellular pathways to direct growth. Here, we identify a distinct mechanism in which adhesion preserves neurite architecture independently of canonical receptor signaling. Using axonal branching in Caenorhabditis elegans PVP interneurons, we show that neuronal SYG-1/Neph1 and epithelial SAX-3/Robo establish a transcellular interface that stabilizes branch orientation and may help resist physiological tissue deformation. This stabilization requires SYG-1 membrane tethering and extracellular domains, but not its cytoplasmic signaling domain, and can be reconstituted with cytoplasmically truncated SYG-1 and SAX-3. The canonical Robo ligand SLT-1 is required for this anchoring mechanism and promotes SYG-1/SAX-3-dependent cell association in vitro. Moreover, an unrelated synthetic adhesion pair partially substitutes for the native receptors and restores branch orientation. These findings reveal a signaling-independent structural role for classical guidance receptors in stabilizing neurite architecture within a deforming tissue environment.
Source: Research Square
Authors: Yun-Hsien Lin, Chun-Hao Chen
Institution: National Taiwan University
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7221789512