Atlastin-1 Summary

Atlastin-1 (ATL1) is a membrane-anchored GTPase that mediates GTP-dependent fusion of endoplasmic reticulum membranes, maintaining the continuous ER network architecture (UniProt: Q8WXF7). The protein functions by forming homodimers on neighboring ER tubules that bind GTP and subsequently undergo conformational changes upon GTP hydrolysis to pull membranes together and drive fusion. After fusion completion and phosphate release, the homodimer disassembles and resets for new fusion cycles. ATL1 may also regulate Golgi biogenesis and indirectly support axonal development.

Mutations in ATL1 cause neurodegenerative disorders including autosomal dominant spastic paraplegia 3 (SPG3) and hereditary sensory neuropathy 1D (HSN1D), both characterized by progressive neurological decline (UniProt: Q8WXF7). These hereditary conditions underscore the protein's critical role in neuronal function and maintenance.

ATL1 is downregulated in Alzheimer's disease brain tissue compared to age-matched controls, with a mean log2 fold-change of −0.725 (Chaparral AD proteomics). This reduction was observed in human post-mortem AD brain analyzed across multiple subcellular fractions using quantitative mass spectrometry, suggesting impaired ER network homeostasis may contribute to AD pathology.