title: Optineurin associates with the podocyte Golgi complex to maintain its structure.
abstract: Optineurin, a cytosolic protein associated with the actin cytoskeleton, microtubules, and the Golgi complex, appears to have an important function in neurons, as mutations in its gene are causative for neurodegenerative diseases such as primary open-angle glaucoma and amyotrophic lateral sclerosis. Here, we report that optineurin is localized in podocytes of the kidney and induced upon injury following treatment with puromycin aminonucleoside. In cultured human podocytes, optineurin localizes to the Golgi complex. Optineurin depletion by RNA interference causes Golgi fragmentation. Moreover, if the Golgi complex is fragmented following microtubule destabilization induced by nocodazole treatment, optineurin dissociates from Golgi vesicles. Furthermore, optineurin colocalizes with vinculin-labeled focal contacts of cultured podocytes and with lysosome-like structures. Optineurin is essential for the survival of cultured podocytes, as optineurin depletion causes cell death. Thus, optineurin appears to play an important role in the maintenance of the podocyte Golgi complex and in the trafficking of vesicles to focal contacts and lysosomes.
authors.affiliation: Institute of Human Anatomy and Embryology, University of Regensburg, Universitätsstrasse 31, 93053, Regensburg, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Sippl
authors.forename: Ludwig F
authors.initials: LF
authors.lastname: Zeilbeck
authors.forename: Rudolf
authors.initials: R
authors.lastname: Fuchshofer
authors.forename: Ernst R
authors.initials: ER
authors.lastname: Tamm
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D018797:Cell Cycle Proteins; D002460:Cell Line; D002470:Cell Survival; D022001:Focal Adhesions / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D008297:Male; D026901:Membrane Transport Proteins; D008870:Microtubules / Q000378:metabolism; D009401:Nephrosis / Q000378:metabolism / Q000473:pathology; D050199:Podocytes / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure*; D011485:Protein Binding; D021381:Protein Transport; D011692:Puromycin Aminonucleoside; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D013347:Subcellular Fractions / Q000378:metabolism; D035582:Transcription Factor TFIIIA / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D026901:Membrane Transport Proteins; C409460:OPTN protein, human; C000598853:OPTN protein, rat; D012333:RNA, Messenger; D035582:Transcription Factor TFIIIA; D042461:Vascular Endothelial Growth Factor A; D011692:Puromycin Aminonucleoside