Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Lysosomal Hydrolases01:22

Lysosomal Hydrolases

4.4K
Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...
4.4K
Delivery Pathways to the Lysosome01:36

Delivery Pathways to the Lysosome

8.7K
Eukaryotic cells use different mechanisms to eliminate toxic waste obsolete and worn-out substances. Lysosomes play a pivotal role in this, and hence, these substances are carried to the lysosome from other parts of the cell and extracellular space through different pathways. The most elaborately studied pathways to the lysosome are the endocytic pathways.
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
8.7K
Cytoskeletal Linker Proteins - Plakins01:09

Cytoskeletal Linker Proteins - Plakins

2.8K
Plakins are large proteins with binding domains for microtubules, microfilaments, intermediate filaments, and membrane-associated protein complexes at cell junctions. Plakin functions are evolutionarily conserved and are primarily involved in organizing the different components of the cytoskeleton by crosslinking them to each other and connecting them to the cell-matrix and cell adhesion complexes. They are also known to interact with signal transducers, serve as scaffolds for signaling...
2.8K
Cystic Fibrosis: Pathogenesis01:23

Cystic Fibrosis: Pathogenesis

670
Cystic fibrosis (CF), an autosomal recessive disorder, significantly affects the function of exocrine glands. This genetically inherited disease is characterized by the production of thick and sticky mucus, which can severely affect various organs and systems in the body.
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
670
Translation01:31

Translation

17.4K
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of Life
Proteins are...
17.4K
Translation01:31

Translation

154.8K
Lesson: Translation
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of...
154.8K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Blood-based RNA-Seq of 5412 individuals with rare disease identifies new candidate diagnoses in the National Genomic Research Library.

medRxiv : the preprint server for health sciences·2026
Same author

Protrudin acts at ER-endosome contacts to promote KIF5-mediated endosomal tubule fission.

Neurobiology of disease·2025
Same author

Exosome Tethering Requires Tetherin Homodimerisation.

Biology of the cell·2025
Same author

The Importance of Lay Navigators in Lung Cancer Screening Among Asian Americans in an Integrated Health Care System.

The Annals of thoracic surgery·2025
Same author

Encephalomyocarditis virus protein 2B* interacts with 14-3-3 proteins through a phosphorylated C-terminal binding motif.

mBio·2025
Same author

Endogenous gene editing of alveolar organoids reveals that expression of pathogenic variant SFTPC-I73T disrupts endosomal function, epithelial polarity and wound healing.

bioRxiv : the preprint server for biology·2025

Related Experiment Video

Updated: Jan 2, 2026

Single-Molecule FRET Imaging for Observing the Conformational Dynamics of Dynamin-Like GTPase Atlastin
10:19

Single-Molecule FRET Imaging for Observing the Conformational Dynamics of Dynamin-Like GTPase Atlastin

Published on: January 24, 2025

921

Spastin MIT Domain Disease-Associated Mutations Disrupt Lysosomal Function.

Rachel Allison1, James R Edgar2, Evan Reid1

  • 1Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom.

Frontiers in Neuroscience
|December 3, 2019
PubMed
Summary

Hereditary spastic paraplegias (HSP) can be caused by mutations in the SPAST gene. This study shows that mutations in spastin's MIT domain disrupt endosomal function, revealing a new disease mechanism beyond microtubule severing.

Keywords:
CHMP1BESCRTIST1endosome tubule fissionhereditary spastic paraplegia

More Related Videos

Aip1p Dynamics Are Altered by the R256H Mutation in Actin
08:57

Aip1p Dynamics Are Altered by the R256H Mutation in Actin

Published on: July 30, 2014

8.3K
Detection of Nuclear Blebbing and DNA Leakage in Mammalian Cells by Immunofluorescence
06:23

Detection of Nuclear Blebbing and DNA Leakage in Mammalian Cells by Immunofluorescence

Published on: January 17, 2025

1.1K

Related Experiment Videos

Last Updated: Jan 2, 2026

Single-Molecule FRET Imaging for Observing the Conformational Dynamics of Dynamin-Like GTPase Atlastin
10:19

Single-Molecule FRET Imaging for Observing the Conformational Dynamics of Dynamin-Like GTPase Atlastin

Published on: January 24, 2025

921
Aip1p Dynamics Are Altered by the R256H Mutation in Actin
08:57

Aip1p Dynamics Are Altered by the R256H Mutation in Actin

Published on: July 30, 2014

8.3K
Detection of Nuclear Blebbing and DNA Leakage in Mammalian Cells by Immunofluorescence
06:23

Detection of Nuclear Blebbing and DNA Leakage in Mammalian Cells by Immunofluorescence

Published on: January 17, 2025

1.1K

Area of Science:

  • Neuroscience
  • Genetics
  • Cell Biology

Background:

  • Hereditary spastic paraplegias (HSPs) are neurodegenerative disorders affecting corticospinal tract axons.
  • Mutations in the SPAST gene, encoding spastin, are a leading genetic cause of HSP, often due to haploinsufficiency.
  • While ATPase domain mutations impair microtubule severing, the role of mutations in the microtubule interacting and trafficking (MIT) domain remains unclear.

Purpose of the Study:

  • To investigate the functional consequences of disease-associated mutations in the spastin MIT domain.
  • To determine if these mutations affect spastin's role in endosomal trafficking and lysosomal function.
  • To elucidate novel molecular mechanisms underlying HSP pathogenesis.

Main Methods:

  • Functional analysis of three spastin MIT domain mutants in cellular models.
  • Assays for endosomal tubule fission, lysosomal enzyme receptor trafficking, and lysosomal morphology.
  • Investigation of spastin's endosomal recruitment and interaction with ESCRT-III proteins.

Main Results:

  • None of the studied spastin MIT mutants supported normal endosomal tubule fission or lysosomal trafficking.
  • One mutant showed impaired endosomal recruitment, while others did not, suggesting non-canonical MIT domain functions.
  • These mutations did not directly impact spastin's microtubule-severing activity.

Conclusions:

  • Spastin MIT domain mutations lead to functional cellular defects relevant to HSP pathogenesis.
  • This study identifies a novel disease mechanism involving impaired endosomal trafficking, independent of microtubule severing.
  • Understanding these non-canonical functions is crucial for developing targeted HSP therapies.