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Cited by 19Neurogenesis and neuroplasticity mechanismsAxon Guidance and Neuronal SignalingProtein Kinase Regulation and GTPase Signaling

MARCKS regulates neuritogenesis and interacts with a CDC42 signaling network

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Brudvig, J. J., Cain, J. T., Sears, R. M., Schmidt-Grimminger, G. G., Wittchen, E. S., Adler, K. B., Ghashghaei, H. T., Weimer, J. M.·2018·Scientific Reports
DOI 10.1038/s41598-018-31578-0PMC PMC6125478
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Abstract

Through the process of neuronal differentiation, newly born neurons change from simple, spherical cells to complex, sprawling cells with many highly branched processes. One of the first stages in this process is neurite initiation, wherein cytoskeletal modifications facilitate membrane protrusion and extension from the cell body. Hundreds of actin modulators and microtubule-binding proteins are known to be involved in this process, but relatively little is known about how upstream regulators bring these complex networks together at discrete locations to produce neurites. Here, we show that Myristoylated alanine-rich C kinase substrate (MARCKS) participates in this process. Marcks−/− cortical neurons extend fewer neurites and have less complex neurite arborization patterns. We use an in vitro proteomics screen to identify MARCKS interactors in developing neurites and characterize an interaction between MARCKS and a CDC42-centered network. While the presence of MARCKS does not affect whole brain levels of activated or total CDC42, we propose that MARCKS is uniquely positioned to regulate CDC42 localization and interactions within specialized cellular compartments, such as nascent neurites.

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  • Rlip associates with MARCKS, a protein that regulates neurite outgrowth via CDC42 network interactions.

    “Studies conducted using neurons have found that Rlip associates with MARCKS, a protein that regulates neurite outgrowth via CDC42 network interactions [111].”

    From Rlip76: An Unexplored Player in Neurodegeneration and Alzheimer’s Disease? (2022) · cites this paper as [111]

    The Results report RALBP1 (Rlip) among MARCKS interactors and identify a MARCKS-associated network centered on CDC42. The Discussion says MARCKS regulates neurite initiation, but treats its influence on CDC42-related activity as a possibility; it does not establish that MARCKS regulates neurite outgrowth *via* those interactions. (LLM, conf=0.83)

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Authors
Brudvig, J. J., Cain, J. T., Sears, R. M., Schmidt-Grimminger, G. G., Wittchen, E. S., Adler, K. B., Ghashghaei, H. T., & Weimer, J. M.
Affiliations
  • University of South Dakota (US)
  • Sanford Research (US)
  • University of North Carolina at Chapel Hill (US)
  • North Carolina State University (US)
Corresponding author
Weimer, J. M.
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2018-09-05
Volume
8
Issue
1
Pages
13278-13278
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-018-31578-0
PMC
PMC6125478
OpenAlex
W2889543808
Cited by
19
References
0
Citations by year
2026: 2 · 2025: 2 · 2024: 4 · 2023: 1 · 2022: 3 · 2021: 4 · 2019: 3
FWCI
0.65
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • U.S. Department of Defense
  • University of South Dakota
  • National Institutes of Health
  • National Defense Science and Engineering Graduate
  • National Institute of General Medical Sciences (P20GM103620, P20GM103548)
  • National Institute of Neurological Disorders and Stroke (R01NS082283, R01NS098370)
Topics
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Keywords
MARCKS, Cdc42, neurite outgrowth, neuronal differentiation, cortical neurons, neurite arborization, protein-protein interaction, actin cytoskeleton, microtubule-binding protein
MeSH terms
Myristoylated Alanine-Rich C Kinase Substrate, Actins, Animals, Cytoskeleton, Female, Male, Mice, Inbred C57BL, Microtubules, Neurons, Phosphorylation, Protein Binding, Pseudopodia, Signal Transduction, Neurites, cdc42 GTP-Binding Protein, Mice, Primary Cell Culture

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