STIM1 Is a MT-Plus-End-Tracking Protein Involved in Remodeling of the ER

Grigoriev, Ilya; Gouveia, Susana Montenegro; Vaart, Babet van der; Demmers, Jeroen; Smyth, Jeremy T.; Honnappa, Srinivas; Splinter, Daniël; Steinmetz, Michel O.; Putney, James W.; Hoogenraad, Casper C.; Akhmanova, Anna

doi:10.1016/j.cub.2007.12.050

Cited by 393 publications

(448 citation statements)

References 17 publications

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“…STIM1 comet-like structures are seen as ER tubules extend with the growing microtubules, but STIM1 comet movements cease after store depletion-induced clustering, indicating that the association with microtubules may be a distinct function from CRAC channel activation (Baba et al, 2006;Grigoriev et al, 2008). In HEK293 cells, microtubule depolymerizaton did decrease CRAC current, but it had little effect on store induced STIM1 clustering (Smyth et al, 2007).…”

Section: Discussionmentioning

confidence: 98%

“…STIM1 colocalizes with tubulin and plays a role in attaching ER membranes to the growing ends of microtubules (Baba et al, 2006;Smyth et al, 2007;Grigoriev et al, 2008), so we reasoned that microtubules might play a role in cap formation. In cells treated with colchicine to disrupt microtubules, STIM1 localized to blebs that protruded from the top of the cell instead of forming a normal cap (Supplemental Figure S4, A and B).…”

Section: An Intact Cytoskeleton Is Required For Normal Cap Formationmentioning

confidence: 99%

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Dynamic Movement of the Calcium Sensor STIM1 and the Calcium Channel Orai1 in Activated T-Cells: Puncta and Distal Caps

Barr

Bernot

Srikanth

et al. 2008

MBoC

129

142

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The proteins STIM1 and Orai1 are the long sought components of the store-operated channels required in T-cell activation. However, little is known about the interaction of these proteins in T-cells after engagement of the T-cell receptor. We found that T-cell receptor engagement caused STIM1 and Orai1 to colocalize in puncta near the site of stimulation and accumulate in a dense structure on the opposite side of the T-cell. FRET measurements showed a close interaction between STIM1 and Orai1 both in the puncta and in the dense cap-like structure. The formation of cap-like structures did not entail rearrangement of the entire endoplasmic reticulum. Cap formation depended on TCR engagement and tyrosine phosphorylation, but not on channel activity or Ca 2؉ influx. These caps were very dynamic in T-cells activated by contact with superantigen pulsed B-cells and could move from the distal pole to an existing or a newly forming immunological synapse. One function of this cap may be to provide preassembled Ca 2؉ channel components to existing and newly forming immunological synapses. INTRODUCTIONT-cell activation in response to antigen induces and requires the elevation of intracellular Ca 2ϩ (Hogan et al., 2003;Quintana et al., 2005;Feske, 2007). T-cell receptor (TCR) engagement leads to activation of well-documented signal transduction pathways that cause a rapid release of Ca 2ϩ from the endoplasmic reticulum (ER; Samelson, 2002;Panyi et al., 2004;Gwack et al., 2007a). The depletion of Ca 2ϩ from this internal store then leads to the opening of ion channels in the plasma membrane (PM) allowing an influx of Ca 2ϩ from outside the cell. The store-operated channel responsible for Ca 2ϩ influx in T-cells is known as the Ca 2ϩ release-activated Ca 2ϩ (CRAC) channel, which has been studied by electrophysiological techniques for many years (Lewis, 2001;Prakriya and Lewis, 2003;Cahalan et al., 2007;Hewavitharana et al., 2007;Hogan and Rao, 2007;Putney, 2007a).Sustained elevation of cytosolic Ca 2ϩ is required for complete T-cell activation (Iezzi et al., 1998;Lewis, 2001;Hogan et al., 2003;Feske, 2007). High levels of intracellular Ca 2ϩ are necessary to maintain the interaction between a T-cell and antigen-presenting cell (APC) that leads to formation of the specialized contact surface known as the immunological synapse (IS). Increased Ca 2ϩ levels are also required for the activation of transcription factors. In particular, elevated Ca 2ϩ maintains prolonged nuclear accumulation of nuclear factor of activated T-cells (NFAT) by activating the phosphatase calcineurin that dephosphorylates NFAT, allowing it to translocate to the nucleus and activate genes such as IL2 (Hogan et al., 2003;Macian, 2005). Several hours of Ca 2ϩ influx are required to complete the T-cell activation program, which involves expression of a large number of activation-associated genes (Lewis, 2001;Macian et al., 2002;Hogan et al., 2003).Although sustained Ca 2ϩ influx in T-cells has been studied for decades, the proteins involved have only been ident...

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Section: Discussionmentioning

confidence: 98%

Section: An Intact Cytoskeleton Is Required For Normal Cap Formationmentioning

confidence: 99%

Dynamic Movement of the Calcium Sensor STIM1 and the Calcium Channel Orai1 in Activated T-Cells: Puncta and Distal Caps

Barr

Bernot

Srikanth

et al. 2008

MBoC

129

142

View full text Add to dashboard Cite

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“…The mechanism and proteins involved in regulating ER movement during mitosis are not well understood; however, it was recently shown that phosphorylation of STIM1 is required to prevent the ER membrane from associating with the mitotic spindle (Smyth et al 2012). STIM1 is an integral membrane protein that binds to EB1, a microtubule (MT) plus tip binding protein, that will be further discussed in a subsequent section (Grigoriev et al 2008). During mitosis, STIM1 is phosphorylated, resulting in dissociation from EB1.…”

Section: Er During Mitosismentioning

confidence: 99%

“…TAC movements depend on tethering between the ER protein, STIM1, and an MT plus end-binding protein, EB1 (Fig. 3B, top panel) (Grigoriev et al 2008). The ER sliding mechanism accounts for the majority of ER dynamics in the cell and occurs through a machinery involving kinesin-1 and dynein MT motors that pull ER tubules along the sides of established MTs (Wozniak et al 2009).…”

Section: Er Dynamics and Assemblymentioning

confidence: 99%

Endoplasmic Reticulum Structure and Interconnections with Other Organelles

English

Voeltz

2013

Cold Spring Harbor Perspectives in Biology

294

220

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The endoplasmic reticulum (ER) is a large, continuous membrane-bound organelle comprised of functionally and structurally distinct domains including the nuclear envelope, peripheral tubular ER, peripheral cisternae, and numerous membrane contact sites at the plasma membrane, mitochondria, Golgi, endosomes, and peroxisomes. These domains are required for multiple cellular processes, including synthesis of proteins and lipids, calcium level regulation, and exchange of macromolecules with various organelles at ER-membrane contact sites. The ER maintains its unique overall structure regardless of dynamics or transfer at ER-organelle contacts. In this review, we describe the numerous factors that contribute to the structure of the ER.T he endoplasmic reticulum (ER) is a dynamic organelle responsible for many cellular functions, including the synthesis of proteins and lipids, and regulation of intracellular calcium levels. This review focuses on the distinct and complex morphology of the ER. The structure of the ER is complex because of the numerous distinct domains that exist within one continuous membrane bilayer. These domains are shaped by interactions with the cytoskeleton, by proteins that stabilize membrane shape, and by a homotypic fusion machinery that allows the ER membrane to maintain its continuity and identity. The ER also contains domains that contact the plasma membrane (PM) and other organelles including the Golgi, endosomes, mitochondria, lipid droplets, and peroxisomes. ER contact sites with other organelles and the PM are both abundant and dispersed throughout the cytoplasm, suggesting that they too could influence the overall architecture of the ER. As we will discuss here, ER shape and distribution are regulated by many intrinsic and extrinsic forces. ER STRUCTURE AND FORMATION Domains of the ER Are Stabilized by Membrane-Shaping ProteinsThe endoplasmic reticulum (ER) is a large membrane-bound compartment spread throughout the cytoplasm of eukaryotic cells. It is divided into three major morphologies that include the nuclear envelope (NE), peripheral ER cisternae, and an interconnected tubular network

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“…When growing microtubules cross the ER, the microtubule tip-binding protein EB1 binds to STIM1 and pulls out a new ER tubule through a "tip attachment complex" mechanism (Grigoriev et al 2008;Honnappa et al 2009). Although this interaction is weakened by store depletion and does not appear necessary for puncta formation (Grigoriev et al 2008), one could imagine that STIM1-laden ER tubules are propelled in this way toward the cell periphery by microtubules, and when they encounter local sites of elevated IP 3 , local ER depletion releases the tubule near the PM with STIM1 primed to interact with the PM and establish or stabilize a junction. Interestingly, in two EM studies, store depletion caused the number of ER-PM junctions to increase, and overexpression of STIM1 further amplified this effect Orci et al 2009).…”

Section: Accumulation Of Stim At Er-pm Junctionsmentioning

confidence: 99%

Store-Operated Calcium Channels: New Perspectives on Mechanism and Function

Lewis¹

2011

Cold Spring Harbor Perspectives in Biology

178

201

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Store-operated calcium channels (SOCs) are a nearly ubiquitous Ca 2þ entry pathway stimulated by numerous cell surface receptors via the reduction of Ca 2þ concentration in the ER. The discovery of STIM proteins as ER Ca 2þ sensors and Orai proteins as structural components of the Ca 2þ release-activated Ca 2þ (CRAC) channel, a prototypic SOC, opened the floodgates for exploring the molecular mechanism of this pathway and its functions. This review focuses on recent advances made possible by the use of STIM and Orai as molecular tools. I will describe our current understanding of the store-operated Ca 2þ entry mechanism and its emerging roles in physiology and disease, areas of uncertainty in which further progress is needed, and recent findings that are opening new directions for research in this rapidly growing field.

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STIM1 Is a MT-Plus-End-Tracking Protein Involved in Remodeling of the ER

Cited by 393 publications

References 17 publications

Dynamic Movement of the Calcium Sensor STIM1 and the Calcium Channel Orai1 in Activated T-Cells: Puncta and Distal Caps

Dynamic Movement of the Calcium Sensor STIM1 and the Calcium Channel Orai1 in Activated T-Cells: Puncta and Distal Caps

Endoplasmic Reticulum Structure and Interconnections with Other Organelles

Store-Operated Calcium Channels: New Perspectives on Mechanism and Function

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