The MCPH7 Gene Product STIL Is Essential for Dendritic Spine Formation Article Swipe
Tohru Matsuki
,
Hidenori Tabata
,
Masashi Ueda
,
Hideaki Ito
,
Koh‐ichi Nagata
,
Yumi Tsuneura
,
Shima Eda
,
Kenji Kasai
,
Atsuo Nakayama
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.3390/cells14020062
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.3390/cells14020062
Dendritic spine formation/maintenance is highly dependent on actin cytoskeletal dynamics, which is regulated by small GTPases Rac1 and Cdc42 through their downstream p21-activated kinase/LIM-kinase-I/cofilin pathway. ARHGEF7, also known as ß-PIX, is a guanine nucleotide exchange factor for Rac1 and Cdc42, thereby activating Rac1/Cdc42 and the downstream pathway, leading to the upregulation of spine formation/maintenance. We found that STIL, one of the primary microcephaly gene products, is associated with ARHGEF7 in dendritic spines and that knockdown of Stil resulted in a significant reduction in dendritic spines in neurons both in vitro and in vivo. Rescue experiments indicated that the STIL requirement for spine formation/maintenance depended on its coiled coil domain that mediates the association with ARHGEF7. The overexpression of Rac1/Cdc42 compensated for the spine reduction caused by STIL knockdown. FRET experiments showed that Rac activation is impaired in STIL knockdown neurons. Chemical long-term potentiation, which triggers Rac activation, promoted STIL accumulation in the spine and its association with ARHGEF7. The dynamics of these proteins further supported their coordinated involvement in spine formation/maintenance. Based on these findings, we concluded that the centrosomal protein STIL is a novel regulatory factor essential for spine formation/maintenance by activating Rac and its downstream pathway, possibly through the association with ARHGEF7.
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- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.3390/cells14020062
- https://www.mdpi.com/2073-4409/14/2/62/pdf?version=1736236430
- OA Status
- gold
- Cited By
- 1
- References
- 49
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4406123963
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Raw OpenAlex JSON
- OpenAlex ID
-
https://openalex.org/W4406123963Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.3390/cells14020062Digital Object Identifier
- Title
-
The MCPH7 Gene Product STIL Is Essential for Dendritic Spine FormationWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2025Year of publication
- Publication date
-
2025-01-07Full publication date if available
- Authors
-
Tohru Matsuki, Hidenori Tabata, Masashi Ueda, Hideaki Ito, Koh‐ichi Nagata, Yumi Tsuneura, Shima Eda, Kenji Kasai, Atsuo NakayamaList of authors in order
- Landing page
-
https://doi.org/10.3390/cells14020062Publisher landing page
- PDF URL
-
https://www.mdpi.com/2073-4409/14/2/62/pdf?version=1736236430Direct link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://www.mdpi.com/2073-4409/14/2/62/pdf?version=1736236430Direct OA link when available
- Concepts
-
Cell biology, Dendritic spine, CDC42, Guanine nucleotide exchange factor, RAC1, Gene knockdown, Cofilin, Chemistry, Actin cytoskeleton, Biology, Kinase, GTPase, Cytoskeleton, Signal transduction, Biochemistry, Gene, Cell, Neuroscience, Hippocampal formationTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
1Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 1Per-year citation counts (last 5 years)
- References (count)
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49Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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| primary_location.landing_page_url | https://doi.org/10.3390/cells14020062 |
| publication_date | 2025-01-07 |
| publication_year | 2025 |
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