Dynein motor contributes to stress granule dynamics in primary neurons

• Published in: Neuroscience Vol. 159; no. 2; pp. 647 - 656
• Main Authors: Tsai, N.-P, Tsui, Y.-C, Wei, L.-N
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 17.03.2009; Elsevier
• Subjects: Adenine - analogs & derivatives; Adenine - pharmacology; Adenylyl Imidodiphosphate - pharmacology; Animals; Animals, Newborn; Antigens, Surface - metabolism; Arsenites - pharmacology; Biological and medical sciences; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cell Count - methods; Cells, Cultured; Cysteine - metabolism; Cytoplasmic Granules - drug effects; Cytoplasmic Granules - metabolism; Dose-Response Relationship, Drug; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; dynein; Dyneins; ELAV Proteins; ELAV-Like Protein 1; Endopeptidase K - pharmacology; Enzyme Inhibitors - pharmacology; Fundamental and applied biological sciences. Psychology; Indoles; Methionine - metabolism; Motor Neurons - cytology; Motor Neurons - drug effects; Motor Neurons - physiology; mRNA; neurites; Neurology; Nonlinear Dynamics; primary neurons; Protein Subunits - metabolism; Protein Transport - drug effects; Rats; RNA, Messenger - genetics; RNA, Messenger - metabolism; RNA, Small Interfering - pharmacology; RNA-Binding Proteins - metabolism; Spinal Cord; stress granules; Stress, Physiological - drug effects; Stress, Physiological - physiology; Sulfur Isotopes - metabolism; Teratogens - pharmacology; Time Factors; translation; Vertebrates: nervous system and sense organs; HSP70; 5′-(β, γ-imido) triphosphate; HuR; kappa opioid receptor; ribonucleoprotein; stress granule; primary neurons; T cell internal antigen 1; mRNA; DLC2A; KOR; dynein; erythro-9-[3-(2-hydroxynonyl)] adenine; TIA-1; SG; RNP; EHNA; dynein light chain 2 A; translation; stress granules; neurites; heat shock protein 70; Hu antigen R; AMP-PNP; Neurite; Granule neuron; Enzyme; Hydrolases; Dynein ATPase; Stress
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2008.12.053

Abstract Mobilization and translation of mRNAs, two important events believed to involve stress granules (SGs), in neurons are important for their survival and activities. However, the formation and disassembly of SGs in neurons remains unclear. By using an arsenite-induced neuronal stress model of rat primary spinal cord neuron cultures, we demonstrate the formation of SGs that contain common SG components and RNAs in both stressed neuronal cell bodies and their neurites. By employing small interfering RNA (siRNA) knockdown, we discovered that dynein motor subunit localizes in SG, and is important for SG assembly in neurons. Under stress, dynein motor subunit also facilitates translational repression and enhances the formation and integrity of SG in neurons. By blocking the energy source of dynein motor, both the formation and disassembly of SG are attenuated. These findings demonstrate, for the first time, that dynein motor complex plays a critical role in the dynamics of neuronal SGs, as well as translation of certain mRNAs.