title: Protrudin binds atlastins and endoplasmic reticulum-shaping proteins and regulates network formation.
abstract: Hereditary spastic paraplegias are inherited neurological disorders characterized by progressive lower-limb spasticity and weakness. Although more than 50 genetic loci are known [spastic gait (SPG)1 to -57], over half of hereditary spastic paraplegia cases are caused by pathogenic mutations in four genes encoding proteins that function in tubular endoplasmic reticulum (ER) network formation: atlastin-1 (SPG3A), spastin (SPG4), reticulon 2 (SPG12), and receptor expression-enhancing protein 1 (SPG31). Here, we show that the SPG33 protein protrudin contains hydrophobic, intramembrane hairpin domains, interacts with tubular ER proteins, and functions in ER morphogenesis by regulating the sheet-to-tubule balance and possibly the density of tubule interconnections. Protrudin also interacts with KIF5 and harbors a Rab-binding domain, a noncanonical FYVE (Fab-1, YGL023, Vps27, and EEA1) domain, and a two phenylalanines in an acidic tract (FFAT) domain and, thus, may also function in the distribution of ER tubules via ER contacts with the plasma membrane or other organelles.
authors: Cell Biology Section, Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
authors: Jaerak
authors: J
authors: Chang
authors: Seongju
authors: S
authors: Lee
authors: Craig
authors: C
authors: Blackstone
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism* / Q000648:ultrastructure; D019204:GTP-Binding Proteins / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism; D050505:Mutant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics / Q000378:metabolism; D000074181:Spastin; D033921:Vesicular Transport Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D050505:Mutant Proteins; D011994:Recombinant Proteins; D033921:Vesicular Transport Proteins; C513390:ZFYVE27 protein, human; C440006:ATL1 protein, human; D000251:Adenosine Triphosphatases; D019204:GTP-Binding Proteins; D000074181:Spastin; C400283:SPAST protein, human
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