Unveiling the Functional Role of KIF21B in Microglia Inflammatory Response
Danny Ganchala1,2, Alvaro Bautista-Abad1,2, Daniel Pinto-Benito1,2
1Centro de Neurociencias Cajal, CSIC, Madrid, Spain.
Glia
|July 9, 2026
Summary
The kinesin KIF21B plays a sex-specific role in microglial (brain immune cell) function. Its regulation impacts cell migration and phagocytosis, influencing brain immune responses differently in males and females.
Area of Science:
- Neuroimmunology
- Cell Biology
- Neuroinflammation
Background:
- Microglia are crucial brain immune cells involved in homeostasis and injury response.
- Cytoskeletal remodeling is essential for microglial functions like migration and phagocytosis.
- The kinesin KIF21B's role in microglial activation and function remains largely unexplored.
Purpose of the Study:
- To investigate the role of KIF21B in microglial activation and function.
- To determine if KIF21B expression and function in microglia are sex-dependent.
- To elucidate the impact of KIF21B on microglial morphology, migration, and phagocytosis.
Main Methods:
- Assessed KIF21B expression in vivo in TBI and LPS-induced neuroinflammation models.
- Utilized primary cultured mouse microglia to investigate KIF21B function.
- Performed KIF21B gene silencing (downregulation) to assess functional consequences.
- Quantified microglial morphology, migration, and phagocytosis.
- Examined KIF21B colocalization with cytoskeletal components (microtubules and F-actin).
Main Results:
- KIF21B expression increased in female microglia around TBI lesions but not after LPS administration.
- KIF21B silencing impaired migration and phagocytosis in female microglia.
- In male microglia, KIF21B silencing enhanced migration and neuronal debris phagocytosis.
- Morphological changes were sex-specific: KIF21B silencing blocked amoeboid transition in females and induced elongation in males.
- LPS treatment altered KIF21B-cytoskeleton interactions in females but not males.
Conclusions:
- KIF21B regulates microglial function in a sex-dependent manner.
- KIF21B influences microglial migration, phagocytosis, and morphology through cytoskeletal organization.
- Findings highlight the importance of sex as a biological variable in neuroinflammatory responses and KIF21B's potential as a therapeutic target.
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