biostudies-literatureFeng YScience and Technology Commission of Shanghai MunicipalityMOST | National Natural Science Foundation of China (NSFC)ShanghaiTech University (ShanghaiTech)National Natural Science Foundation of ChinaShanghaiTech UniversityMOST | National Natural Science Foundation of China7477-7512https://www.ebi.ac.uk/biostudies/studies/S-EPMC12706091biostudies-literatureUnknown44(24)Directed axonal trafficking of mRNA via ribonucleoprotein (RNP) complexes is essential for neuronal function and survival. However, mechanisms governing retrograde RNP transport remain poorly understood. Here, we reveal that Annexin A7 (ANXA7) promotes the recruitment of aggregation-prone T-cell intracellular antigen 1 (TIA1)-containing RNPs to cytoplasmic dynein, enabling their retrograde trafficking to the soma for degradation. Both persistent and transient Ca²⁺ elevation disrupted this function of ANXA7, leading to the detachment of TIA1 granules from dynein, impairing their transport, and subsequently triggering pathological TIA1 aggregation within axons. Similarly, ANXA7 knockdown decouples TIA1 granules from dynein, preventing their transport and inducing pathological aggregation of The EMBO journalAnnexin A7 enhances TIA1 axonal trafficking to counteract pathological aggregation in neurons.PMC1270609132370604322710012449071380032100777SYLDX0302022SYLPOC0022022Wan SPan XLiu YLi JLuan TZhang ZFeng YDou KWang TChu YWang WXu YfalseAnnexin A7 enhances TIA1 axonal trafficking to counteract pathological aggregation in neurons.Directed axonal trafficking of mRNA via ribonucleoprotein (RNP) complexes is essential for neuronal function and survival. However, mechanisms governing retrograde RNP transport remain poorly understood. Here, we reveal that Annexin A7 (ANXA7) promotes the recruitment of aggregation-prone T-cell intracellular antigen 1 (TIA1)-containing RNPs to cytoplasmic dynein, enabling their retrograde trafficking to the soma for degradation. Both persistent and transient Ca²⁺ elevation disrupted this function of ANXA7, leading to the detachment of TIA1 granules from dynein, impairing their transport, and subsequently triggering pathological TIA1 aggregation within axons. Similarly, ANXA7 knockdown decouples TIA1 granules from dynein, preventing their transport and inducing pathological aggregation of 2025-01-01T00:00:00Z2025 Dec2026-07-15T06:33:46.99Z2026-06-30T03:23:24.332ZS-EPMC127060914118864710.1038/s44318-025-00609-8