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Gα13 Contributes to LPS-Induced Morphological Alterations and Affects Migration of Microglia

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Abstract

Microglia are the resident immune cells of the CNS that are activated in response to a variety of stimuli. This phenotypical change is aimed to maintain the local homeostasis, also by containing the insults and repair the damages. All these processes are tightly regulated and coordinated and a failure in restoring homeostasis by microglia can result in the development of neuroinflammation that can facilitate the progression of pathological conditions. Indeed, chronic microglia activation is commonly recognized as a hallmark of many neurological disorders, especially at an early stage. Many complex pathways, including cytoskeletal remodeling, are involved in the control of the microglial phenotypical and morphological changes that occur during activation. In this work, we focused on the small GTPase Gα13 and its role at the crossroad between RhoA and Rac1 signaling when microglia is exposed to pro-inflammatory stimulation. We propose the direct involvement of Gα13 in the cytoskeletal rearrangements mediated by FAK, LIMK/cofilin, and Rac1 during microglia activation. In fact, we show that Gα13 knockdown significantly inhibited LPS-induced microglial cell activation, in terms of both changes in morphology and migration, through the modulation of FAK and one of its downstream effectors, Rac1. In conclusion, we propose Gα13 as a critical factor in the regulation of morphological and functional properties of microglia during activation, which might become a target of intervention for the control of microglia inflammation.

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Acknowledgements

Part of this work was carried out in ALEMBIC, the advanced microscopy laboratory established by the San Raffaele Scientific Institute and University.

Funding

This work was carried out within the framework of the NeOn project (ID 239047 to DZ), with the financial support of Regione Lombardia (POR FESR 2014 – 2020), and the Ivascomar project (CTN01_00177_165430 to DZ), Cluster Tecnologico Nazionale Scienze della Vita “Alisei”, Italian Ministry of Research.

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Author notes

  1. Barbara Bettegazzi and Serena Bellani contributed equally to this work.

Authors and Affiliations

  1. IRCCS San Raffaele Scientific Institute, via Olgettina 60, 20132, Milan, Italy

    Barbara Bettegazzi, Serena Bellani, Stefano Cattaneo, Franca Codazzi, Fabio Grohovaz & Daniele Zacchetti

  2. Vita-Salute San Raffaele University, via Olgettina 58, 20132, Milan, Italy

    Barbara Bettegazzi, Stefano Cattaneo, Franca Codazzi & Fabio Grohovaz

Authors
  1. Barbara Bettegazzi
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  2. Serena Bellani
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  3. Stefano Cattaneo
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  4. Franca Codazzi
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  5. Fabio Grohovaz
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  6. Daniele Zacchetti
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Contributions

Conceptualization, SB, BB, DZ; resources, DZ; data curation, SB, BB, SC; writing–original draft preparation, SB; writing–review and editing, SB, BB, FG, FC, DZ; all authors read and approved the final manuscript.

Corresponding authors

Correspondence to Barbara Bettegazzi or Daniele Zacchetti.

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Ethics Approval

All animal experiments have been carried out following the ARRIVE guidelines and in accordance with the EU Directive 2010/63/EU for animal experiments. The study was approved by the Institutional Animal Care and Use Committee of the San Raffaele Scientific Institute (number 752, 2016).

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The authors declare no competing interests.

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Bettegazzi, B., Bellani, S., Cattaneo, S. et al. Gα13 Contributes to LPS-Induced Morphological Alterations and Affects Migration of Microglia. Mol Neurobiol 58, 6397–6414 (2021). https://doi.org/10.1007/s12035-021-02553-0

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  • DOI: https://doi.org/10.1007/s12035-021-02553-0

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