title: STIM1 is a MT-plus-end-tracking protein involved in remodeling of the ER.
abstract: Stromal interaction molecule 1 (STIM1) is a transmembrane protein that is essential for store-operated Ca(2+) entry, a process of extracellular Ca(2+) influx in response to the depletion of Ca(2+) stores in the endoplasmic reticulum (ER) (reviewed in [1-4]). STIM1 localizes predominantly to the ER; upon Ca(2+) release from the ER, STIM1 translocates to the ER-plasma membrane junctions and activates Ca(2+) channels (reviewed in [1-4]). Here, we show that STIM1 directly binds to the microtubule-plus-end-tracking protein EB1 and forms EB1-dependent comet-like accumulations at the sites where polymerizing microtubule ends come in contact with the ER network. Therefore, the previously observed tubulovesicular motility of GFP-STIM1 [5] is not a motor-based movement but a traveling wave of diffusion-dependent STIM1 concentration in the ER membrane. STIM1 overexpression strongly stimulates ER extension occurring through the microtubule "tip attachment complex" (TAC) mechanism [6, 7], a process whereby an ER tubule attaches to and elongates together with the EB1-positive end of a growing microtubule. Depletion of STIM1 and EB1 decreases TAC-dependent ER protrusion, indicating that microtubule growth-dependent concentration of STIM1 in the ER membrane plays a role in ER remodeling.
authors.affiliation: Department of Cell Biology, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands.
authors.forename: Ilya
authors.initials: I
authors.lastname: Grigoriev
authors.forename: Susana Montenegro
authors.initials: SM
authors.lastname: Gouveia
authors.forename: Babet
authors.initials: B
authors.lastname: van der Vaart
authors.forename: Jeroen
authors.initials: J
authors.lastname: Demmers
authors.forename: Jeremy T
authors.initials: JT
authors.lastname: Smyth
authors.forename: Srinivas
authors.initials: S
authors.lastname: Honnappa
authors.forename: Daniël
authors.initials: D
authors.lastname: Splinter
authors.forename: Michel O
authors.initials: MO
authors.lastname: Steinmetz
authors.forename: James W
authors.initials: JW
authors.lastname: Putney
authors.forename: Casper C
authors.initials: CC
authors.lastname: Hoogenraad
authors.forename: Anna
authors.initials: A
authors.lastname: Akhmanova
mesh_terms: D002118:Calcium / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D000071737:Stromal Interaction Molecule 1
chemical_list: C500985:MAPRE1 protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; C103530:STIM1 protein, human; D000071737:Stromal Interaction Molecule 1; D002118:Calcium