دورية أكاديمية
أعرض في EDS

Palmitoylation controls the stability of 190 kDa ankyrin-G in dendritic spines and is regulated by ZDHHC8 and lithium.

التفاصيل البيبلوغرافية
العنوان: Palmitoylation controls the stability of 190 kDa ankyrin-G in dendritic spines and is regulated by ZDHHC8 and lithium.
المؤلفون: Piguel NH; Department of Neuroscience, Northwestern University Feinberg School of Medicine, Chicago, IL, United States., Sanders SS; Shriners Hospitals Pediatric Research Center, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United States., De Simone FI; Shriners Hospitals Pediatric Research Center, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United States., Martin-de-Saavedra MD; Department of Neuroscience, Northwestern University Feinberg School of Medicine, Chicago, IL, United States.; Department of Biochemistry and Molecular Biology, School of Pharmacy, Instituto Universitario de Investigación en Neuroquímica, Complutense University of Madrid, Madrid, Spain., McCoig E; Department of Neuroscience, Northwestern University Feinberg School of Medicine, Chicago, IL, United States., Dionisio LE; Department of Neuroscience, Northwestern University Feinberg School of Medicine, Chicago, IL, United States., Smith KR; Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO, United States., Thomas GM; Department of Anatomy and Cell Biology, Shriners Hospitals Pediatric Research Center, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, United States., Penzes P; Department of Neuroscience, Northwestern University Feinberg School of Medicine, Chicago, IL, United States.; Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, United States.; Northwestern University Center for Autism and Neurodevelopment, Chicago, IL, United States.
المصدر: Frontiers in molecular neuroscience [Front Mol Neurosci] 2023 Mar 08; Vol. 16, pp. 1144066. Date of Electronic Publication: 2023 Mar 08 (Print Publication: 2023).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Frontiers Research Foundation Country of Publication: Switzerland NLM ID: 101477914 Publication Model: eCollection Cited Medium: Print ISSN: 1662-5099 (Print) Linking ISSN: 16625099 NLM ISO Abbreviation: Front Mol Neurosci Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: Lausanne, Switzerland : Frontiers Research Foundation, 2008-
مستخلص: Introduction: AnkG, encoded by the ANK3 gene, is a multifunctional scaffold protein with complex isoform expression: the 480 and 270 kDa isoforms have roles at the axon initial segment and node of Ranvier, whereas the 190 kDa isoform (AnkG-190) has an emerging role in the dendritic shaft and spine heads. All isoforms of AnkG undergo palmitoylation, a post-translational modification regulating protein attachment to lipid membranes. However, palmitoylation of AnkG-190 has not been investigated in dendritic spines. The ANK3 gene and altered expression of AnkG proteins are associated with a variety of neuropsychiatric and neurodevelopmental disorders including bipolar disorder and are implicated in the lithium response, a commonly used mood stabilizer for bipolar disorder patients, although the precise mechanisms involved are unknown.
Result: Here, we showed that Cys70 palmitoylation stabilizes the localization of AnkG-190 in spine heads and at dendritic plasma membrane nanodomains. Mutation of Cys70 impairs AnkG-190 function in dendritic spines and alters PSD-95 scaffolding. Interestingly, we find that lithium reduces AnkG-190 palmitoylation thereby increasing its mobility in dendritic spines. Finally, we demonstrate that the palmitoyl acyl transferase ZDHHC8, but not ZDHHC5, increases AnkG-190 stability in spine heads and is inhibited by lithium.
Discussion: Together, our data reveal that palmitoylation is critical for AnkG-190 localization and function and a potential ZDHHC8/AnkG-190 mechanism linking AnkG-190 mobility to the neuronal effects of lithium.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2023 Piguel, Sanders, De Simone, Martin-de-Saavedra, McCoig, Dionisio, Smith, Thomas and Penzes.)
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معلومات مُعتمدة: R01 MH107182 United States MH NIMH NIH HHS
فهرسة مساهمة: Keywords: ANK3; ZDHHC8; ankyrin-G; dendrite; dendritic spine; lithium; palmitoylation
تواريخ الأحداث: Date Created: 20230327 Latest Revision: 20240224
رمز التحديث: 20240224
مُعرف محوري في PubMed: PMC10031057
DOI: 10.3389/fnmol.2023.1144066
PMID: 36969554
قاعدة البيانات: MEDLINE
الوصف
تدمد:1662-5099
DOI:10.3389/fnmol.2023.1144066