The endoplasmic reticulum Ca2+-ATPase SERCA2b is upregulated in activated microglia and its inhibition causes opposite effects on migration and phagocytosis Morales-Ropero, Juan M Arroyo-Urea, Sandra Neubrand, Veronika Elisabeth Martín Oliva, Francisco David Marín Teva, José Luis Cuadros Ojeda, Miguel Ángel Vangheluwe, Peter Navascues Martínez, Julio Mata, Ana M Sepúlveda Justo, María Del Rosario Alzheimer's disease Brain Calcium pump This is the peer reviewed version of the following article: Morales-Ropero JM, Arroyo-Urea S, Neubrand VE, Martín-Oliva D, Marín-Teva JL, Cuadros MA, Vangheluwe P, Navascués J, Mata AM, Sepúlveda MR. The endoplasmic reticulum Ca2+ -ATPase SERCA2b is upregulated in activated microglia and its inhibition causes opposite effects on migration and phagocytosis. Glia. 2021 Apr;69(4):842-857, which has been published in final form at https://onlinelibrary.wiley.com/doi/10.1002/glia.23931. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited. The accepted version is under embargo until April 2022. Activation of microglia is an early immune response to damage in the brain. Although a key role for Ca2+ as trigger of microglial activation has been considered, little is known about the molecular scenario for regulating Ca2+ homeostasis in these cells. Taking into account the importance of the endoplasmic reticulum as a cellular Ca2+ store, the sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA2b) is an interesting target to modulate intracellular Ca2+ dynamics. We found upregulation of SERCA2b in activated microglia of human brain with Alzheimer´s disease and we further studied the participation of SERCA2b in microglial functions by using the BV2 murine microglial cell line and primary microglia isolated from mouse brain. To trigger microglia activation, we used the bacterial lipopolysaccharide (LPS), which is known to induce an increase of cytosolic Ca2+. Our results showed an upregulated expression of SERCA2b in LPS-induced activated microglia likely associated to an attempt to restore the increased cytosolic Ca2+ concentration. We analyzed SERCA2b contribution in microglial migration by using the specific SERCA inhibitor thapsigargin in scratch assays. Microglial migration was strongly stimulated with thapsigargin, even more than with LPS-induction, but delayed in time. However, phagocytic capacity of microglia was blocked in the presence of the SERCA inhibitor, indicating the importance of a tight control of cytosolic Ca2+ in these processes. All together, these results provide for the first time compelling evidence for SERCA2b as a major player regulating microglial functions, affecting migration and phagocytosis in an opposite manner. 2024-01-02T12:12:14Z 2024-01-02T12:12:14Z 2021 journal article Glia 69: 842–857 https://hdl.handle.net/10481/86487 10.1002/glia.23931 eng http://creativecommons.org/licenses/by-nc-nd/3.0/ open access Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License Wiley