AI Article Synopsis
- The study investigates the role of endosomal SNARE proteins Vti1a and Vti1b in neuronal development, highlighting their importance for membrane fusion and neurite outgrowth.
- In a mouse model and using CRISPR/Cas9, the researchers created a double knockout of these proteins in neuroblastoma cells, which showed impaired differentiation and reduced neurite formation compared to normal cells.
- The findings indicate that the absence of these SNARE proteins hinders critical signaling pathways involved in neurite elongation, specifically affecting responses to neurotrophic factors and signaling cascades like Akt and Erk.
Article Abstract
During intracellular trafficking N-ethylmaleimide-sensitive-factor attachment receptor (SNARE) proteins catalyze the membrane fusion by assembling into a four-helix complex. In the mouse model, loss of the endosomal SNAREs vti1a and vti1b results in a perinatal lethal phenotype and neuronal defects including decreased neurite outgrowth in cultured primary neurons. We used a CRISPR/Cas9 system to generate a Vti1a Vti1b double knockout (DKO) in the neuroblastoma cell line N1E-115. Three different DKO cell lines were obtained and examined at genome and protein level. The double deficiency impaired proper differentiation based on lower levels of synaptic proteins as well as reduced neurite formation and elongation compared to wild type cells in differentiation medium. Neurite elongation can be induced by a variety of extracellular signals via different signaling cascades. Treatment with the Rho kinase inhibitor Y27632, which stimulates enlargeosome exocytosis, or with neurotrophic factors (BDNF, NGF and NT3) resulted in reduced stimulation of all DKO clones and in significantly shorter neurites compared to wild type cells. The loss of vti1a and vti1b disrupted Akt signaling during enlargeosome-mediated and Erk signaling during BDNF-induced neurite outgrowth.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.ejcb.2024.151461 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
The double deficiency of the SNARE proteins vti1a and vti1b affects neurite outgrowth and signaling in N1E-115 neuroblastoma cells.
Eur J Cell Biol
December 2024
Biochemistry III, Department of Chemistry, Bielefeld University, Universitätsstraße 25, Bielefeld 33615, Germany. Electronic address:
Article Synopsis
- The study investigates the role of endosomal SNARE proteins Vti1a and Vti1b in neuronal development, highlighting their importance for membrane fusion and neurite outgrowth.
- In a mouse model and using CRISPR/Cas9, the researchers created a double knockout of these proteins in neuroblastoma cells, which showed impaired differentiation and reduced neurite formation compared to normal cells.
- The findings indicate that the absence of these SNARE proteins hinders critical signaling pathways involved in neurite elongation, specifically affecting responses to neurotrophic factors and signaling cascades like Akt and Erk.
Synaptotagmin-11 regulates immune functions of microglia in vivo.
J Neurochem
December 2023
Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, China.
Membrane trafficking pathways mediate key microglial activities such as cell migration, cytokine secretion, and phagocytosis. However, the underlying molecular mechanism remains poorly understood. Previously, we found that synaptotagmin-11 (Syt11), a non-Ca -binding Syt associated with Parkinson's disease (PD) and schizophrenia, inhibits cytokine release and phagocytosis in primary microglia.
View Article and Find Full Text PDFPrimary neurons lacking the SNAREs vti1a and vti1b show altered neuronal development.
Neural Dev
November 2022
Biochemistry III, Department of Chemistry, Bielefeld University, Bielefeld, Germany.
Background: Neurons are highly specialized cells with a complex morphology generated by various membrane trafficking steps. They contain Golgi outposts in dendrites, which are formed from somatic Golgi tubules. In trafficking membrane fusion is mediated by a specific combination of SNARE proteins.
View Article and Find Full Text PDFThe SNARE protein Vti1b is recruited to the sites of BCR activation but is redundant for antigen internalisation, processing and presentation.
Front Cell Dev Biol
August 2022
Institute of Biomedicine, and MediCity Research Laboratories, University of Turku, Turku, Finland.
In order to fulfil the special requirements of antigen-specific activation and communication with other immune cells, B lymphocytes require finely regulated endosomal vesicle trafficking. How the endosomal machinery is regulated in B cells remains largely unexplored. In our previous proximity proteomic screen, we identified the SNARE protein Vti1b as one of the strongest candidates getting accumulated to the sites of early BCR activation.
View Article and Find Full Text PDFAblation of Vti1a/1b Triggers Neural Progenitor Pool Depletion and Cortical Layer 5 Malformation in Late-embryonic Mouse Cortex.
Neuroscience
May 2021
Institute for Neuroanatomy, University Medical Center, Georg-August-University Göttingen, Göttingen, Germany. Electronic address:
Cortical morphogenesis entails several neurobiological events, including proliferation and differentiation of progenitors, migration of neuroblasts, and neuronal maturation leading to functional neural circuitry. These neurodevelopmental processes are delicately regulated by many factors. Endosomal SNAREs have emerged as formidable modulators of neuronal growth, aside their well-known function in membrane/vesicular trafficking.
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!