Axons of the corpus callosum (CC), the white matter tract that connects the left and right hemispheres of the brain, receive instruction from a number of chemoattractant and chemorepulsant cues during their initial navigation towards and across the midline. While it has long been known that the CC is malformed in the absence of Myristoylated alanine-rich C-kinase substrate (MARCKS), evidence for a direct role of MARCKS in axon navigation has been lacking. Here, we show that MARCKS is necessary for Netrin-1 (NTN1) signaling through the DCC receptor, which is critical for axon guidance decisions. Marcks null (Marcks) neurons fail to respond to exogenous NTN1 and are deficient in markers of DCC activation. Without MARCKS, the subcellular distributions of two critical mediators of NTN1-DCC signaling, the tyrosine kinases PTK2 and SRC, are disrupted. Together, this work establishes a novel role for MARCKS in axon dynamics and highlights the necessity of MARCKS as an organizer of DCC signaling at the membrane.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6139093 | PMC |
| http://dx.doi.org/10.1007/s12035-018-0990-3 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Machine Learning Reveals Aneuploidy Characteristics in Cancers: The Impact of BEX4.
Front Biosci (Landmark Ed)
November 2024
Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, 230022 Hefei, Anhui, China.
Background: Aneuploidy is crucial yet under-explored in cancer pathogenesis. Specifically, the involvement of brain expressed X-linked gene 4 () in microtubule formation has been identified as a potential aneuploidy mechanism. Nevertheless, 's comprehensive impact on aneuploidy incidence across different cancer types remains unexplored.
View Article and Find Full Text PDFMarcks overexpression in retinal ganglion cells promotes optic nerve regeneration.
Cell Death Dis
December 2024
Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Regeneration of injured central nervous system (CNS) axons is highly restricted, leading to permanent neurological deficits. The myristoylated alanine-rich C-kinase substrate (MARCKS) is a membrane-associated protein kinase C (PKC) substrate ubiquitously expressed in eukaryotic cells, plays critical roles in development, brain plasticity, and tissues regeneration. However, little is known about the role of Marcks in CNS axon regeneration.
View Article and Find Full Text PDFIn vascular smooth muscle cells (VSMCs) and vascular endothelial cells (VECs), phosphatidylinositol 4,5-bisphosphate (PIP) acts as a substrate for phospholipase C (PLC)- and phosphoinositol 3-kinase (PI3K)-mediated signaling pathways and an unmodified ligand at ion channels and other macromolecules, which are key processes in the regulation of cell physiological and pathological phenotypes. It is envisaged that these distinct roles of PIP are achieved by PIP-binding proteins, which act as PIP buffers to produce discrete pools of PIP that permits targeted release within the cell. This review discusses evidence for the expression, cell distribution, and role of myristoylated alanine-rich C-kinase substrate (MARCKS), a PIP-binding protein, in cellular signaling and function of VSMCs.
View Article and Find Full Text PDFThe Formation of Human Arteriovenous Malformation Organoids and Their Characteristics.
Cells
November 2024
Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea.
Article Synopsis
- AVMs are abnormal connections between arteries and veins that lack capillaries, and there is a limited understanding of their diagnosis and treatment, along with a lack of in vitro models for study.
- This research developed 2D endothelial cell cultures and 3D blood vessel organoids (BVOs) to compare gene expression, revealing that AVM organoids had higher levels of angiogenesis-related genes like FSTL1 and hsa-mir-135b-5p.
- The created AVM organoids can be used as effective models to explore disease mechanisms and test potential therapies, advancing insights for developing treatment strategies for AVMs.
Predicting prognosis in lung adenocarcinoma by predicting TIGIT expression: a pathomics model.
J Thorac Dis
November 2024
Department of Thoracic Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China.
Background: Traditional diagnostic methods have limited efficacy in predicting the prognosis of lung adenocarcinoma (LUAD), T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) is a new biomarker. This study aimed to evaluate TIGIT expression as a LUAD biomarker and predict patient prognosis using a pathological feature model.
Methods: Clinical data and pathological images from The Cancer Genome Atlas (TCGA) were analyzed.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!