PMID- 11102458 OWN - NLM STAT- MEDLINE DCOM- 20010208 LR - 20231104 IS - 1529-2401 (Electronic) IS - 0270-6474 (Print) IS - 0270-6474 (Linking) VI - 20 IP - 23 DP - 2000 Dec 1 TI - Neurobeachin: A protein kinase A-anchoring, beige/Chediak-higashi protein homolog implicated in neuronal membrane traffic. PG - 8551-65 AB - We describe the identification and initial characterization of neurobeachin, a neuron-specific multidomain protein of 327 kDa with a high-affinity binding site (K(d), 10 nm) for the type II regulatory subunit of protein kinase A (PKA RII). Neurobeachin is peripherally associated with pleomorphic tubulovesicular endomembranes near the trans sides of Golgi stacks and throughout the cell body and cell processes. It is also found in a subpopulation of synapses, where it is concentrated at the postsynaptic plasma membrane. In live cells, perinuclear neurobeachin is dispersed by brefeldin A (BFA) within 1 min, and in permeabilized cells a recruitment of neurobeachin from cytosol to Golgi-near membranes is stimulated by GTPgammaS and prevented by brefeldin A. Spots of neurobeachin recruitment are close to but distinct from recruitment sites of COP-I, AP-1, and AP-3 coat proteins involved in vesicle budding. These observations indicate that neurobeachin binding to membranes close to the trans-Golgi requires an ADP-ribosylation factor-like GTPase, possibly in association with a novel type of protein coat. A neurobeachin isoform that does not bind RII, beige-like protein (BGL), is expressed in many tissues. Neurobeachin, BGL, and approximately 10 other mammalian gene products share a characteristic C-terminal BEACH-WD40 sequence module, which is also present in gene products of invertebrates, plants, protozoans, and yeasts, thus defining a new protein family. The prototype member of this family of BEACH domain proteins, lysosomal trafficking regulator (LYST), is deficient in genetic defects of protein sorting in lysosome biogenesis (the beige mouse and Chediak-Higashi syndrome). Neurobeachin's subcellular localization, its coat protein-like membrane recruitment, and its sequence similarity to LYST suggest an involvement in neuronal post-Golgi membrane traffic, one of its functions being to recruit protein kinase A to the membranes with which it associates. FAU - Wang, X AU - Wang X AD - Institut fur Physiologische Chemie and Institut fur Anatomie, Ruhr-Universitat Bochum, D-44780 Bochum, Germany. FAU - Herberg, F W AU - Herberg FW FAU - Laue, M M AU - Laue MM FAU - Wullner, C AU - Wullner C FAU - Hu, B AU - Hu B FAU - Petrasch-Parwez, E AU - Petrasch-Parwez E FAU - Kilimann, M W AU - Kilimann MW LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Neurosci JT - The Journal of neuroscience : the official journal of the Society for Neuroscience JID - 8102140 RN - 0 (Carrier Proteins) RN - 0 (Helminth Proteins) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (Lyst protein, mouse) RN - 0 (Lyst protein, rat) RN - 0 (Membrane Proteins) RN - 0 (Nbea protein, mouse) RN - 0 (Nerve Tissue Proteins) RN - 0 (Protein Synthesis Inhibitors) RN - 0 (Proteins) RN - 0 (Vesicular Transport Proteins) RN - 0 (che-2 protein, C elegans) RN - 20350-15-6 (Brefeldin A) RN - 37589-80-3 (Guanosine 5'-O-(3-Thiotriphosphate)) RN - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinase Type II) RN - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases) SB - IM MH - Animals MH - Binding Sites/genetics MH - Brefeldin A/pharmacology MH - COP-Coated Vesicles/metabolism MH - COS Cells MH - Carrier Proteins/*genetics/metabolism MH - Chediak-Higashi Syndrome/*genetics MH - Chickens MH - Cloning, Molecular MH - Cyclic AMP-Dependent Protein Kinase Type II MH - Cyclic AMP-Dependent Protein Kinases/*metabolism MH - Cytosol/metabolism MH - Golgi Apparatus/drug effects/metabolism MH - Guanosine 5'-O-(3-Thiotriphosphate)/pharmacology MH - Helminth Proteins/genetics MH - Intracellular Membranes/metabolism MH - Intracellular Signaling Peptides and Proteins MH - Membrane Proteins MH - Mice MH - Nerve Tissue Proteins/*genetics/metabolism MH - Neurons/cytology/drug effects/*metabolism MH - PC12 Cells MH - Protein Structure, Tertiary/genetics MH - Protein Synthesis Inhibitors/pharmacology MH - Protein Transport/drug effects/genetics MH - Proteins/*genetics MH - Rats MH - Sequence Homology, Amino Acid MH - Vesicular Transport Proteins PMC - PMC6773050 EDAT- 2000/01/11 19:15 MHDA- 2001/03/03 10:01 PMCR- 2001/06/01 CRDT- 2000/01/11 19:15 PHST- 2000/01/11 19:15 [pubmed] PHST- 2001/03/03 10:01 [medline] PHST- 2000/01/11 19:15 [entrez] PHST- 2001/06/01 00:00 [pmc-release] AID - 20/23/8551 [pii] AID - 4693 [pii] AID - 10.1523/JNEUROSCI.20-23-08551.2000 [doi] PST - ppublish SO - J Neurosci. 2000 Dec 1;20(23):8551-65. doi: 10.1523/JNEUROSCI.20-23-08551.2000.