The hereditary spastic paraplegias comprise a group of inherited neurological disorders in which the primary manifestation is spastic weakness of the lower extremities. Troyer syndrome is an autosomal recessive form of spastic paraplegia caused by a frameshift mutation in the spartin (SPG20) gene. Currently, neither the localization nor the functions of the spartin protein are known. In this study, we generated anti-spartin antibodies and found that spartin is both cytosolic and membrane-associated. Using a yeast two-hybrid approach, we screened an adult human brain library for binding partners of spartin. We identified Eps15, a protein known to be involved in endocytosis and the control of cell proliferation. This interaction was confirmed by fusion protein "pull-down" experiments as well as a cellular redistribution assay. Our results suggest that spartin might be involved in endocytosis, vesicle trafficking, or mitogenic activity, and that impairment in one of these processes may underlie the long axonopathy in patients with Troyer syndrome.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bbrc.2005.06.201 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Protocol for generating and characterizing a nasal epithelial model using imaging with application for respiratory viruses.
STAR Protoc
January 2025
Department of Microbiology and Immunology, Schulich School of Medicine & Dentistry, Western University, London, ON, Canada. Electronic address:
Air-liquid interface (ALI) culture can differentiate airway epithelial cells to recapitulate the respiratory tract in vitro. Here, we present a protocol for isolating and culturing nasal epithelial cells from turbinate tissues for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We describe steps to overcome challenges of imaging fragile cultures, detect the production of mucus, and quantify intracellular virus post-SARS-CoV-2 infection.
View Article and Find Full Text PDFA framework for translating tauopathy therapeutics: Drug discovery to clinical trials.
Alzheimers Dement
November 2024
Rainwater Charitable Foundation, Fort Worth, Texas, USA.
The tauopathies are defined by pathological tau protein aggregates within a spectrum of clinically heterogeneous neurodegenerative diseases. The primary tauopathies meet the definition of rare diseases in the United States. There is no approved treatment for primary tauopathies.
View Article and Find Full Text PDFSpartin is a Lipid Transfer Protein That Facilitates Lipid Droplet Turnover.
Contact (Thousand Oaks)
May 2024
UCL Institute of Ophthalmology, University College London, London, UK.
One means by which cells reutilize neutral lipids stored in lipid droplets is to degrade them by autophagy. This process involves spartin, mutations of which cause the rare inherited disorder Troyer syndrome (or spastic paraplegia-20, SPG20). A recently published paper from the team led by Karin Reinsich (Yale) suggests that the molecular function of spartin and its unique highly conserved "senescence" domain is as a lipid transfer protein.
View Article and Find Full Text PDFLysosomal damage sensing and lysophagy initiation by SPG20-ITCH.
Mol Cell
April 2024
Center of Medical Biotechnology, Faculty of Biology, University of Duisburg-Essen, Essen, Germany. Electronic address:
Cells respond to lysosomal membrane permeabilization by membrane repair or selective macroautophagy of damaged lysosomes, termed lysophagy, but it is not fully understood how this decision is made. Here, we uncover a pathway in human cells that detects lipid bilayer perturbations in the limiting membrane of compromised lysosomes, which fail to be repaired, and then initiates ubiquitin-triggered lysophagy. We find that SPG20 binds the repair factor IST1 on damaged lysosomes and, importantly, integrates that with the detection of damage-associated lipid-packing defects of the lysosomal membrane.
View Article and Find Full Text PDFLateralizing calcaneal osteotomy performed with a percutaneous burr results in a significantly lower increase in tarsal tunnel pressure.
Eur J Orthop Surg Traumatol
May 2024
Department of Orthopaedic Surgery, Mayo Clinic Florida, Jacksonville, FL, USA.
Purpose: Tarsal tunnel syndrome is well documented following lateralizing calcaneal osteotomy to manage varus hindfoot deformity. Traditionally, calcaneal osteotomy is performed with an oscillating saw. No studies have investigated the effect of alternative surgical techniques on postoperative tarsal tunnel pressure.
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!