Phosphorylation of STIM1 at ERK/CDK sites is dispensable for cell migration and ER partitioning in mitosis
<p dir="ltr">Store-operated Ca<sup>2+</sup> entry (SOCE) is a ubiquitous Ca<sup>2+</sup> influx pathway required for multiple physiological functions including cell motility. SOCE is triggered in response to depletion of intracellular Ca<sup>2+</sup&g...
محفوظ في:
| المؤلف الرئيسي: | |
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| مؤلفون آخرون: | , , , , |
| منشور في: |
2021
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| الموضوعات: | |
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| _version_ | 1864513551787360256 |
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| author | Ayat S. Hammad (9592374) |
| author2 | Fang Yu (156838) Welathanthrige S. Botheju (17151175) Asha Elmi (9592371) Ethel Alcantara-Adap (14152851) Khaled Machaca (194372) |
| author2_role | author author author author author |
| author_facet | Ayat S. Hammad (9592374) Fang Yu (156838) Welathanthrige S. Botheju (17151175) Asha Elmi (9592371) Ethel Alcantara-Adap (14152851) Khaled Machaca (194372) |
| author_role | author |
| dc.creator.none.fl_str_mv | Ayat S. Hammad (9592374) Fang Yu (156838) Welathanthrige S. Botheju (17151175) Asha Elmi (9592371) Ethel Alcantara-Adap (14152851) Khaled Machaca (194372) |
| dc.date.none.fl_str_mv | 2021-12-01T00:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1016/j.ceca.2021.102496 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Phosphorylation_of_STIM1_at_ERK_CDK_sites_is_dispensable_for_cell_migration_and_ER_partitioning_in_mitosis/24314374 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biological sciences Biochemistry and cell biology Store-operated calcium entry Mitosis Endoplasmic reticulum Cell migration Calcium Signaling STIM1 |
| dc.title.none.fl_str_mv | Phosphorylation of STIM1 at ERK/CDK sites is dispensable for cell migration and ER partitioning in mitosis |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">Store-operated Ca<sup>2+</sup> entry (SOCE) is a ubiquitous Ca<sup>2+</sup> influx pathway required for multiple physiological functions including cell motility. SOCE is triggered in response to depletion of intracellular Ca<sup>2+</sup> stores following the activation of the endoplasmic reticulum (ER) Ca<sup>2+</sup> sensor STIM1, which recruits the plasma membrane (PM) Ca<sup>2+</sup> channel Orai1 at ER-PM junctions. STIM1 is phosphorylated dynamically, and this phosphorylation has been implicated in several processes including SOCE inactivation during M-phase, maximal SOCE activation, ER segregation during mitosis, and cell migration. Human STIM1 has 10 Ser/Thr residues in its cytosolic domain that match the ERK/CDK consensus phosphorylation. We recently generated a mouse knock-in line where wild-type STIM1 was replaced by a non-phosphorylatable STIM1 with all ten S/Ts mutated to Ala (STIM1–10A). Here, we generate mouse embryonic fibroblasts (MEF) from the STIM1–10A mouse line and a control MEF line (WT) that express wild-type STIM1 from a congenic mouse strain. These lines offer a unique model to address the role of STIM1 phosphorylation at endogenous expression levels in contrast to previous studies that relied mostly on overexpression. We show that STIM1 phosphorylation at ERK/CDK sites is not required for SOCE activation, cell migration, or ER partitioning during mitosis. These results rule out STIM1 phosphorylation as a regulator of SOCE, migration, and ER distribution in mitosis.</p><h2>Other Information</h2><p dir="ltr">Published in: Cell Calcium<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1016/j.ceca.2021.102496" target="_blank">https://dx.doi.org/10.1016/j.ceca.2021.102496</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_552eb98d71647bd3a8c6eb2dea8cc541 |
| identifier_str_mv | 10.1016/j.ceca.2021.102496 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/24314374 |
| publishDate | 2021 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Phosphorylation of STIM1 at ERK/CDK sites is dispensable for cell migration and ER partitioning in mitosisAyat S. Hammad (9592374)Fang Yu (156838)Welathanthrige S. Botheju (17151175)Asha Elmi (9592371)Ethel Alcantara-Adap (14152851)Khaled Machaca (194372)Biological sciencesBiochemistry and cell biologyStore-operated calcium entryMitosisEndoplasmic reticulumCell migrationCalcium SignalingSTIM1<p dir="ltr">Store-operated Ca<sup>2+</sup> entry (SOCE) is a ubiquitous Ca<sup>2+</sup> influx pathway required for multiple physiological functions including cell motility. SOCE is triggered in response to depletion of intracellular Ca<sup>2+</sup> stores following the activation of the endoplasmic reticulum (ER) Ca<sup>2+</sup> sensor STIM1, which recruits the plasma membrane (PM) Ca<sup>2+</sup> channel Orai1 at ER-PM junctions. STIM1 is phosphorylated dynamically, and this phosphorylation has been implicated in several processes including SOCE inactivation during M-phase, maximal SOCE activation, ER segregation during mitosis, and cell migration. Human STIM1 has 10 Ser/Thr residues in its cytosolic domain that match the ERK/CDK consensus phosphorylation. We recently generated a mouse knock-in line where wild-type STIM1 was replaced by a non-phosphorylatable STIM1 with all ten S/Ts mutated to Ala (STIM1–10A). Here, we generate mouse embryonic fibroblasts (MEF) from the STIM1–10A mouse line and a control MEF line (WT) that express wild-type STIM1 from a congenic mouse strain. These lines offer a unique model to address the role of STIM1 phosphorylation at endogenous expression levels in contrast to previous studies that relied mostly on overexpression. We show that STIM1 phosphorylation at ERK/CDK sites is not required for SOCE activation, cell migration, or ER partitioning during mitosis. These results rule out STIM1 phosphorylation as a regulator of SOCE, migration, and ER distribution in mitosis.</p><h2>Other Information</h2><p dir="ltr">Published in: Cell Calcium<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1016/j.ceca.2021.102496" target="_blank">https://dx.doi.org/10.1016/j.ceca.2021.102496</a></p>2021-12-01T00:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1016/j.ceca.2021.102496https://figshare.com/articles/journal_contribution/Phosphorylation_of_STIM1_at_ERK_CDK_sites_is_dispensable_for_cell_migration_and_ER_partitioning_in_mitosis/24314374CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/243143742021-12-01T00:00:00Z |
| spellingShingle | Phosphorylation of STIM1 at ERK/CDK sites is dispensable for cell migration and ER partitioning in mitosis Ayat S. Hammad (9592374) Biological sciences Biochemistry and cell biology Store-operated calcium entry Mitosis Endoplasmic reticulum Cell migration Calcium Signaling STIM1 |
| status_str | publishedVersion |
| title | Phosphorylation of STIM1 at ERK/CDK sites is dispensable for cell migration and ER partitioning in mitosis |
| title_full | Phosphorylation of STIM1 at ERK/CDK sites is dispensable for cell migration and ER partitioning in mitosis |
| title_fullStr | Phosphorylation of STIM1 at ERK/CDK sites is dispensable for cell migration and ER partitioning in mitosis |
| title_full_unstemmed | Phosphorylation of STIM1 at ERK/CDK sites is dispensable for cell migration and ER partitioning in mitosis |
| title_short | Phosphorylation of STIM1 at ERK/CDK sites is dispensable for cell migration and ER partitioning in mitosis |
| title_sort | Phosphorylation of STIM1 at ERK/CDK sites is dispensable for cell migration and ER partitioning in mitosis |
| topic | Biological sciences Biochemistry and cell biology Store-operated calcium entry Mitosis Endoplasmic reticulum Cell migration Calcium Signaling STIM1 |