4.6 Review

The myristoylated alanine-rich C-kinase substrates (MARCKS): A membrane-anchored mediator of the cell function

Journal

AUTOIMMUNITY REVIEWS
Volume 20, Issue 11, Pages -

Publisher

ELSEVIER
DOI: 10.1016/j.autrev.2021.102942

Keywords

Protein kinase C; Cell function; Inflammation; Immune modulation; Autoimmunity; Schizophrenia; Psychosis; Dementia; Cancer; Personalized medicine

Categories

Funding

  1. China Scholarship Council, China [201906210461]
  2. Pinnacle Research Award in Liver Disease from American Association for the Study of Liver Diseases (AASLD)
  3. NIH [R01DK123262]

Ask authors/readers for more resources

MARCKS and MARCKSL1 are membrane-associated proteins involved in various cellular processes. MARCKS plays a critical role in the sequestration and release of phosphatidylinositol-4,5-diphosphate (PIP2), and is associated with immune function, cancer, psychiatric disorders, and autoimmune diseases.
The myristoylated alanine-rich C-kinase substrate (MARCKS) and the MARCKS-related protein (MARCKSL1) are ubiquitous, highly conserved membrane-associated proteins involved in the structural modulation of the actin cytoskeleton, chemotaxis, motility, cell adhesion, phagocytosis, and exocytosis. MARCKS includes an N-terminal myristoylated domain for membrane binding, a highly conserved MARCKS Homology 2 (MH2) domain, and an effector domain (which is the phosphorylation site). MARCKS can sequester phosphatidylinositol-4, 5-diphosphate (PIP2) at lipid rafts in the plasma membrane of quiescent cells, an action reversed by protein kinase C (PKC), ultimately modulating the immune function. Being expressed mostly in innate immune cells, MARCKS promotes the inflammation-driven migration and adhesion of cells and the secretion of cytokines such as tumor necrosis factor (TNF). From a clinical point of view, MARCKS is overexpressed in patients with schizophrenia and bipolar disorders, while the brain level of MARCKS phosphorylation is associated with Alzheimer's disease. Furthermore, MARCKS is associated with the development and progression of numerous types of cancers. Data in autoimmune diseases are limited to rheumatoid arthritis models in which a connection between MARCKS and the JAK-STAT pathway is mediated by miRNAs. We provide a comprehensive overview of the structure of MARCKS, its molecular characteristics and functions from a biological and pathogenetic standpoint, and will discuss the clinical implications of this pathway.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.6
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available