<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "Mechanisms of STIM1-mediated endoplasmic reticulum-plasma membrane (ER-PM) contact formation"^^ . "The coupling of endoplasmic reticulum (ER) and plasma membrane (PM) is crucial for\r\ncalcium (Ca2+) homeostasis. STIM1 and STIM2 are type I membrane proteins of the ER and\r\nfunction as Ca2+ sensors in a process known as store-operated calcium entry (SOCE). They\r\nsense a drop in luminal Ca2+ concentration and undergo conformational changes and\r\noligomerization. The active oligomerized STIM proteins translocate to ER-PM contact sites,\r\nwhere they bind to phosphoinositides (PIPs) at the inner leaflet of the PM via their lysine (K)-\r\nrich domains and activate Orai1, a pore-forming Ca2+ release-activated Ca2+ (CRAC)\r\nchannel subunit in the PM.\r\nI found that STIM2, but not STIM1, contains a di-lysine ER-retention signal. This\r\nsignal restricts the function of STIM2 as Ca2+ sensor to the ER while STIM1 can reach the\r\nPM via the classical secretary pathway. The intracellular distribution of STIM1 is regulated in\r\na cell-cycle-dependent manner with cell surface expression of STIM1 during mitosis.\r\nEfficient retention of STIM1 in the ER during interphase depends on its K-rich domain and a\r\ndi-arginine ER retention signal. SOCE enhances ER retention, suggesting that trafficking of\r\nSTIM1 is regulated and this regulation contributes to STIM1’s role as multifunctional\r\ncomponent in Ca2+-signaling.\r\nIn contrast to mitotic cells, interphase cells retain most of their STIM1 intracellularly.\r\nUnder resting condition, the ER-resident STIMs are preferentially located in PI(4,5)P2\r\ncontaining preexisting ER-PM contact sites, which are expanded upon ER Ca2+ depletion.\r\nThe lipid-binding, K-rich domains are required to localize STIM proteins in preexisting ERPM\r\ncontact sites. Moreover, STIM2 recruits ER more efficiently to the PM. This is consistent\r\nwith the fact that STIM2 has higher lipid-binding affinity and lower activation threshold than\r\nSTIM1 and that STIM2 functions as a regulator of basal Ca2+ homeostasis.\r\nFinally, I studied the role of microtubules in ER-PM contact site formation. I observed\r\nthat STIM1 aligns along microtubules. Alignment of STIM proteins with microtubules is a\r\nconserved process. In addition to accumulation of STIM1 at microtubule plus ends, STIM1\r\nmoves along microtubules in an EB-1-independent manner. I identified two EB-1-\r\nindependent microtubule-binding sites located within the C-terminus of STIM1 and found\r\nthat oligomerization increases the EB-1-independent microtubule-binding affinity of STIM1.\r\nHowever, the physiological function of this EB1-independent microtubule binding activity\r\nremains elusive."^^ . "2014" . . . . . . . "Shan-Hua"^^ . "Chung"^^ . "Shan-Hua Chung"^^ . . . . . . "Mechanisms of STIM1-mediated endoplasmic reticulum-plasma membrane (ER-PM) contact formation (PDF)"^^ . . . "thesis_final_20140620.pdf"^^ . . . "Mechanisms of STIM1-mediated endoplasmic reticulum-plasma membrane (ER-PM) contact formation (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "Mechanisms of STIM1-mediated endoplasmic reticulum-plasma membrane (ER-PM) contact formation (Other)"^^ . . . . . . "preview.jpg"^^ . . . "Mechanisms of STIM1-mediated endoplasmic reticulum-plasma membrane (ER-PM) contact formation (Other)"^^ . . . . . . "medium.jpg"^^ . . . "Mechanisms of STIM1-mediated endoplasmic reticulum-plasma membrane (ER-PM) contact formation (Other)"^^ . . . . . . "small.jpg"^^ . . . "Mechanisms of STIM1-mediated endoplasmic reticulum-plasma membrane (ER-PM) contact formation (Other)"^^ . . . . . . "indexcodes.txt"^^ . . "HTML Summary of #17515 \n\nMechanisms of STIM1-mediated endoplasmic reticulum-plasma membrane (ER-PM) contact formation\n\n" . "text/html" . . . "500 Naturwissenschaften und Mathematik"@de . "500 Natural sciences and mathematics"@en . . . "570 Biowissenschaften, Biologie"@de . "570 Life sciences"@en . .