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Cited by 27Neuroinflammation and Neurodegeneration MechanismsCell Adhesion Molecules ResearchNeurogenesis and neuroplasticity mechanisms

Integrin-Kindlin3 requirements for microglial motility in vivo are distinct from those for macrophages

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Meller, Julia, Chen, Zhihong, Dudiki, Tejasvi, Cull, Rebecca M., Murtazina, Rakhilya, Bal, Saswat K., Pluskota, Elzbieta, Stefl, Samantha +3 more·2017·JCI Insight
DOI 10.1172/jci.insight.93002PMC PMC5453700
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Abstract

Microglia play a critical role in the development and homeostasis of the CNS. While mobilization of microglia is critical for a number of pathologies, understanding of the mechanisms of their migration in vivo is limited and often based on similarities to macrophages. Kindlin3 deficiency as well as Kindlin3 mutations of integrin-binding sites abolish both integrin inside-out and outside-in signaling in microglia, thereby resulting in severe deficiencies in cell adhesion, polarization, and migration in vitro, which are similar to the defects observed in macrophages. In contrast, while Kindlin3 mutations impaired macrophage mobilization in vivo, they had no effect either on the population of microglia in the CNS during development or on mobilization of microglia and subsequent microgliosis in a model of multiple sclerosis. At the same time, acute microglial response to laser-induced injury was impaired by the lack of Kindlin3-integrin interactions. Based on 2-photon imaging of microglia in the brain, Kindlin3 is required for elongation of microglial processes toward the injury site and formation of phagosomes in response to brain injury. Thus, while Kindlin3 deficiency in human subjects is not expected to diminish the presence of microglia within CNS, it might delay the recovery process after injury, thereby exacerbating its complications.

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  • Focal adhesions are positioned at critical junctions of cells, linking the extracellular matrix with the actin cytoskeleton and allowing microglia to efficiently survey the parenchyma and respond to injuries.

    “Focal adhesions are positioned at critical junctions of cellslinking the extracellular matrix with the actin cytoskeletonand allowing microglia to efficiently survey the parenchyma and respond to injuries (Choi et al., 2015; Meller et al., 2017).”

    From Alzheimer’s genetic risk factor CASS4 controls microglial focal adhesion biology and amyloidosis (2026) · cites this paper as Meller et al., 2017

    The section on Kindlin3–integrin interaction says adhesion complexes bridge the cytoskeleton and extracellular matrix in migrating cells. The Introduction describes microglial surveillance, and the injury-response results link Kindlin3-related adhesion signaling to movement toward injury. Our copy does not establish that focal adhesions enable efficient surveillance of the parenchyma, so the claimed causal link goes beyond the evidence. (LLM, conf=0.84)

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Cited by

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Authors
Meller, J., Chen, Z., Dudiki, T., Cull, R. M., Murtazina, R., Bal, S. K., Pluskota, E., Stefl, S., Plow, E. F., Trapp, B. D., & Byzova, T. V.
Affiliations
  • Department of Molecular Cardiology and
  • Cleveland Clinic (US)
Corresponding author
Byzova, Tatiana V.
ORCID
Venue
JCI Insight
Publisher
American Society for Clinical Investigation
Published
2017-06-02
Volume
2
Issue
11
ISSN
2379-3708 (ISSN-L)
DOI
10.1172/jci.insight.93002
PMC
PMC5453700
OpenAlex
W2621129590
Cited by
27
References
8
Citations by year
2026: 1 · 2025: 1 · 2024: 3 · 2023: 1 · 2022: 5 · 2021: 4 · 2020: 5 · 2019: 4 · 2018: 3
FWCI
1.63
Type
journal article
Language
en
Open access
Locations
  • JCI Insight (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Heart, Lung, and Blood Institute (R01HL096062, P01HL073311, R01HL071625)
  • National Center for Research Resources (S10RR026820)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Keywords
integrins, microglial migration, macrophages, microglial activation, multiple sclerosis, phagosome formation, microglial polarization, cell adhesion, central nervous system development

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