biostudies-literatureWang ZHNIAMS NIH HHS636-48https://www.ebi.ac.uk/biostudies/studies/S-EPMC4434815biostudies-literatureUnknown4(5)Drosophila Clueless (Clu) and its conserved orthologs are known for their role in the prevention of mitochondrial clustering. Here, we uncover a new role for Clu in the delivery of integrin subunits in muscle tissue. In clu mutants, αPS2 integrin, but not βPS integrin, abnormally accumulates in a perinuclear endoplasmic reticulum (ER) subdomain, a site that mirrors the endogenous localization of Clu. Loss of components essential for mitochondrial distribution do not phenocopy the clu mutant αPS2 phenotype. Conversely, RNAi knockdown of the Drosophila Golgi reassembly and stacking protein GRASP55/65 (dGRASP) recapitulates clu defects, including the abnormal accumulation of αPS2 and larval locomotor activity. Both Clu and dGRASP proteins physically interact and loss of Clu displaces dGRASP fBiology openLoss of a Clueless-dGRASP complex results in ER stress and blocks Integrin exit from the perinuclear endoplasmic reticulum in Drosophila larval muscle.PMC4434815R01 AR060788Wang ZHRabouille CGeisbrecht ERfalseLoss of a Clueless-dGRASP complex results in ER stress and blocks Integrin exit from the perinuclear endoplasmic reticulum in Drosophila larval muscle.Drosophila Clueless (Clu) and its conserved orthologs are known for their role in the prevention of mitochondrial clustering. Here, we uncover a new role for Clu in the delivery of integrin subunits in muscle tissue. In clu mutants, αPS2 integrin, but not βPS integrin, abnormally accumulates in a perinuclear endoplasmic reticulum (ER) subdomain, a site that mirrors the endogenous localization of Clu. Loss of components essential for mitochondrial distribution do not phenocopy the clu mutant αPS2 phenotype. Conversely, RNAi knockdown of the Drosophila Golgi reassembly and stacking protein GRASP55/65 (dGRASP) recapitulates clu defects, including the abnormal accumulation of αPS2 and larval locomotor activity. Both Clu and dGRASP proteins physically interact and loss of Clu displaces dGRASP f2015-01-01T00:00:00Z2015 Apr2026-04-29T07:41:06.948Z2025-06-01T01:02:19.785ZS-EPMC44348152586224610.1242/bio.201511551