Alternative splicing transitions occur during organ development, and, in numerous diseases, splicing programs revert to fetal isoform expression. We previously found that extensive splicing changes occur during postnatal mouse heart development in genes encoding proteins involved in vesicle-mediated trafficking. However, the regulatory mechanisms of this splicing-trafficking network are unknown. Here, we found that membrane trafficking genes are alternatively spliced in a tissue-specific manner, with striated muscles exhibiting the highest levels of alternative exon inclusion. Treatment of differentiated muscle cells with chromatin-modifying drugs altered exon inclusion in muscle cells. Examination of several RNA-binding proteins revealed that the poly-pyrimidine tract binding protein 1 (PTBP1) and quaking regulate splicing of trafficking genes during myogenesis, and that removal of PTBP1 motifs prevented PTBP1 from binding its RNA target. These findings enhance our understanding of developmental splicing regulation of membrane trafficking proteins which might have implications for muscle disease pathogenesis.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8925968 | PMC |
| http://dx.doi.org/10.1261/rna.078993.121 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
New Atg9 Phosphorylation Sites Regulate Autophagic Trafficking in Glia.
ASN Neuro
January 2025
School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
We previously identified a role for dAuxilin (dAux), the fly homolog of Cyclin G-associated kinase, in glial autophagy contributing to Parkinson's disease (PD). To further dissect the mechanism, we present evidence here that lack of glial dAux enhanced the phosphorylation of the autophagy-related protein Atg9 at two newly identified threonine residues, T62 and T69. The enhanced Atg9 phosphorylation in the absence of dAux promotes autophagosome formation and Atg9 trafficking to the autophagosomes in glia.
View Article and Find Full Text PDFTracking Cholesterol Flip-Flop in Mammalian Plasma Membrane through Coarse-Grained Molecular Dynamics Simulations.
Langmuir
January 2025
Department of Chemistry, Indian Institute of Technology Delhi, Hauz Khas, New Delhi 110016, India.
Plasma membrane (PM) simulations at longer length and time scales at nearly atomistic resolution can provide invaluable insights into cell signaling, apoptosis, lipid trafficking, and lipid raft formation. We propose a coarse-grained (CG) model of a mammalian PM considering major lipid head groups distributed asymmetrically across the membrane bilayer and validate the model against bilayer structural properties from atomistic simulation. Using the proposed CG model, we identify a recurring pattern in the passive collective cholesterol transbilayer motion and study the individual cholesterol flip-flop events and associated pathways along with lateral ordering in the bilayer during a flip-flop event.
View Article and Find Full Text PDFIdentification of the role of SNARE proteins in rAAV vector production through interaction with the viral MAAP.
Mol Ther Methods Clin Dev
March 2025
Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Adeno-associated virus (AAV) expresses a membrane-associated accessory protein (MAAP), a small nonstructural protein, that facilitates AAV secretion out of the plasma membrane through an association with extracellular vesicles during AAV egress. Here, we investigated the host proteins that interact with AAV2 MAAP (MAAP2) using APEX2-mediated proximity labeling. We identified two SNARE proteins, Syntaxin 7 (STX7) and synaptosome-associated protein 23 (SNAP23), a vesicle (v-)SNARE and a target (t-)SNARE, respectively, that mediate intracellular trafficking of membrane vesicles aand exhibited associations with MAAP2 in HEK293 cells.
View Article and Find Full Text PDFA Dual-Color Fluorescence-Based Ratiometric Assay to Measure Endocytic Trafficking of Surface Proteins.
Methods Mol Biol
January 2025
Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI, USA.
Many membrane proteins on the cell surface are constantly internalized from, and re-delivered to, the plasma membrane. This endocytic cycling, which relies on accurate SNARE-mediated fusion of vesicles containing cargo proteins, is highly important for the function of many proteins such as signaling receptors. While the SNARE proteins that mediate fusion during specific events, such as neurotransmitter and hormone release, in mammalian cells has been heavily studied, the SNARE proteins that mediate surface delivery of specific cargo such as the receptors for these released factors are still not known.
View Article and Find Full Text PDFUse of Biotin-Labeled Geranyl Pyrophosphate for Analysis of Ykt6 Geranylgeranylation.
Methods Mol Biol
January 2025
Department of Molecular and Cellular Biology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
Functionally derivatized analogs of prenyl lipids are valuable tools for the detection and analysis of prenylated proteins. Using a biotinylated analog of geranylgeranyl, we previously identified Ykt6 as a substrate for a novel protein prenyltransferase, termed geranylgeranyltransferase type III (GGTase-III). Ykt6 is an evolutionarily highly conserved SNARE protein that regulates multiple intracellular trafficking pathways, including intra-Golgi trafficking and autophagosome-lysosome fusion.
View Article and Find Full Text PDFWant 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!