ASTN1 (astrotactin 1) is a neuronal cell-surface protein that mediates glial-guided neuronal migration in laminar brain structures, accumulating in the forward aspect of the leading process of migrating cerebellar granule cells where new neuron-glial adhesion sites form PMID:20573900. Its surface levels are governed by a complex with the paralog ASTN2, which controls how much ASTN1 reaches the plasma membrane during migration PMID:20573900, and the cyclical release of adhesions to the glial fiber depends on dynamin-dependent endocytosis of the receptor, since dynamin inhibition rapidly and reversibly arrests migration PMID:20573900. Bi-allelic loss-of-function variants in ASTN1 cause human neurodevelopmental disorders with defects in radial-glia-guided neuronal migration, and ASTN1 genetically interacts with ASTN2 in this pathway PMID:41544630. Beyond its neuronal role, ASTN1 overexpression suppresses migration and invasion of liver cancer cells by inhibiting Wnt/β-catenin signaling, downregulating β-catenin and downstream targets in a manner reversed by the Wnt inhibitor XAV939 PMID:32945491. ASTN1 expression is itself subject to post-transcriptional control by miR-sc3, which directly targets Astn1 mRNA for translational suppression PMID:26786955.
| Year | Confidence | Finding | PMIDs | Journal |
|---|---|---|---|---|
| 2010 | High | ASTN2 forms a protein complex with ASTN1 and regulates its surface expression, controlling the levels of ASTN1 in the plasma membrane during glial-guided neuronal migration. | PMID:20573900 | The Journal of neuroscience |
| 2010 | Medium | ASTN1-Venus accumulates in the forward aspect of the leading process of migrating cerebellar granule cells, where new sites of neuron-glial adhesion form, indicating directional intracellular trafficking of ASTN1 is coupled to neuronal locomotion. | PMID:20573900 | The Journal of neuroscience |
| 2010 | Medium | Dynamin-dependent endocytosis is required for ASTN1 trafficking and neuronal migration: treatment with Dynasore (a Dynamin inhibitor) rapidly and reversibly arrests glial-guided migration of cerebellar granule cells, implicating receptor endocytosis in the release of neuronal adhesions to the glial fiber. | PMID:20573900 | The Journal of neuroscience |
| 2016 | Medium | miR-sc3 directly targets Astn1 mRNA and causes translational suppression of ASTN1, with an inverse expression relationship between miR-sc3 and Astn1 in injured sciatic nerve after transection. | PMID:26786955 | Cell transplantation |
| 2020 | Medium | ASTN1 overexpression in liver cancer cells reduces their migratory and invasive capacity and downregulates β-catenin, TCF1, TCF4, C-jun, C-myc, COX2, MMP2, MMP9, and VEGF protein levels, indicating suppression of Wnt/β-catenin signaling; Wnt inhibitor XAV939 reversed the ASTN1-mediated inhibition of invasion and migration. | PMID:32945491 | Oncology reports |
| 2026 | Medium | Bi-allelic loss-of-function variants in ASTN1 in humans cause neurodevelopmental disorders with defects in radial-glia-guided neuronal migration, and ASTN1 genetically interacts with ASTN2 (one individual had heterozygous variants in both), placing ASTN1 in the same pathway as ASTN2 for neuronal migration. | PMID:41544630 | American journal of human genetics |