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

Destabilization of Microtubules01:45

Destabilization of Microtubules

3.9K
The destabilization of microtubules can occur during different stages of the microtubule lifecycle, such as nucleation or elongation. It can take place at either end of the microtubule or in the microtubule lattices as a whole. The lifespan of individual microtubules within a cell varies according to the cell type and stage of the cell cycle. During interphase, the lifespan of the microtubule is about 30 minutes, while during cell division, it is about 15 minutes. In axonal microtubules of...
3.9K
The Movement of Organelles and Vesicles01:43

The Movement of Organelles and Vesicles

7.2K
In eukaryotic cells,  cytoskeletal filaments such as actin, microtubules, and intermediate filaments form a mesh-like cytoskeletal network. These filaments serve as tracks for transporting cellular cargo. Specialized motor proteins use the chemical energy stored in adenosine triphosphate (ATP) for this transport. During interphase, microtubules are polarized, with the plus-end towards the cell periphery and the minus-end towards the cell center. Two microtubule-associated motor proteins,...
7.2K
Microtubule Instability02:17

Microtubule Instability

6.4K
Microtubules are hollow cylindrical filaments having a diameter of approximately 25 nm and a length that varies from 200 nm to 25 μm. GTP-bound tubulin subunits form αβ-heterodimers for microtubule assembly. These core building blocks interact longitudinally, polymerizing into protofilaments. The protofilaments then interact with one another through lateral bonding forces to form stable cylindrical microtubules. These cylindrical filaments are dynamic as they undergo repeated...
6.4K
Microtubule Instability02:17

Microtubule Instability

6.2K
6.2K
ATP Synthase: Mechanism01:48

ATP Synthase: Mechanism

18.8K
In animals, the mitochondrial F1F0 ATP synthase is the key protein that synthesizes ATP molecules through a complex catalytic mechanism. While the nuclear genome encodes the majority of ATP synthase subunits, the mitochondrial genome encodes some of the enzyme's most critical components. The formation of this multi-subunit enzyme is a complex multi-step process regulated at the level of transcription, translation, and assembly. Defects in one or more of these steps can result in decreased...
18.8K
Intracellular Movement of Viruses and Bacteria01:10

Intracellular Movement of Viruses and Bacteria

3.8K
Intracellular bacteria and viruses often comprise a group of highly infectious pathogens that can cause several diseases. Bacterial pathogens include those belonging to the genus Rickettsia responsible for conditions such as rocky mountain spotted fever and the Mediterranean spotted fever; Chlamydia, a genus responsible for a sexually transmitted disease; Coxiella burnetii, an agent responsible for Q fever. Viral pathogens include vaccinia—a poxvirus, and herpes simplex virus—a...
3.8K

You might also read

Related Articles

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

Sort by
Same author

Beyond Binding Affinity: How a Conformation-Specific Salt Bridge Tunes KIF1A Mechanochemistry.

Cytoskeleton (Hoboken, N.J.)·2026
Same author

The P3018S disease variant reveals how dynein's trailing motor sets ensemble velocity.

bioRxiv : the preprint server for biology·2026
Same author

Publisher Correction: Adaptor-mediated recruitment of three dyneins to dynactin enhances force generation.

Nature cell biology·2026
Same author

Adaptor-mediated recruitment of three dyneins to dynactin enhances force generation.

Nature cell biology·2026
Same author

Pathogenic KIF1A R350 Variants Disrupt A Conserved Kinesin-Tubulin Salt Bridge.

bioRxiv : the preprint server for biology·2025
Same author

Enhanced axonal transport in large vertebrates: KIF5A adaptations in giraffes and pythons.

bioRxiv : the preprint server for biology·2025

Related Experiment Video

Updated: Apr 1, 2026

Identification of Kinesin-1 Cargos Using Fluorescence Microscopy
08:06

Identification of Kinesin-1 Cargos Using Fluorescence Microscopy

Published on: February 14, 2016

8.4K

Pathogenic KIF1A R350 mutations disrupt a conserved and conformation-dependent kinesin-tubulin salt bridge.

Abhipsa Shatarupa1, Lu Rao1, Ana B Asenjo1

  • 1Department of Biochemistry and Gruss-Lipper Biophotonics Center, Albert Einstein College of Medicine, Bronx, NY, USA.

Nature Communications
|March 30, 2026
PubMed
Summary

Pathogenic KIF1A mutations disrupt a key salt bridge with microtubules, altering motor function. This structural insight explains KIF1A-associated neurological disorder (KAND) and offers therapeutic targets.

More Related Videos

Directly Measuring Forces Within Reconstituted Active Microtubule Bundles
07:47

Directly Measuring Forces Within Reconstituted Active Microtubule Bundles

Published on: May 10, 2022

2.0K
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

8.5K

Related Experiment Videos

Last Updated: Apr 1, 2026

Identification of Kinesin-1 Cargos Using Fluorescence Microscopy
08:06

Identification of Kinesin-1 Cargos Using Fluorescence Microscopy

Published on: February 14, 2016

8.4K
Directly Measuring Forces Within Reconstituted Active Microtubule Bundles
07:47

Directly Measuring Forces Within Reconstituted Active Microtubule Bundles

Published on: May 10, 2022

2.0K
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

8.5K

Area of Science:

  • Molecular Biology
  • Neuroscience
  • Structural Biology

Background:

  • Kinesin family member 1A (KIF1A) motor protein mutations cause KIF1A-associated neurological disorder (KAND).
  • Specific mutations at KIF1A residue R350 are linked to hereditary spastic paraplegia and altered motor function.
  • The structural underpinnings of R350-mediated pathogenicity are not well understood.

Purpose of the Study:

  • To elucidate the structural basis of KIF1A R350 mutations in KIF1A-associated neurological disorder (KAND).
  • To investigate the role of the R350 residue in KIF1A's interaction with microtubules and its effect on motor function.

Main Methods:

  • High-resolution cryo-electron microscopy (cryo-EM) to determine structures of KIF1A R350G and R350W mutants bound to microtubules.
  • Biochemical and single-molecule assays to assess motor function, including velocity, processivity, and microtubule affinity.

Main Results:

  • Identified a crucial salt bridge between KIF1A R350 and α-tubulin E415 in the open motor domain conformation.
  • Demonstrated that R350 mutations disrupt this salt bridge.
  • Observed that salt bridge disruption leads to increased velocity, reduced processivity, and decreased microtubule affinity in the apo conformation.

Conclusions:

  • An electrostatic interaction involving KIF1A R350 at the motor-microtubule interface regulates KIF1A motility.
  • Disruption of this interaction by pathogenic mutations provides a structural explanation for KAND.
  • Findings offer potential targets for therapeutic interventions in KIF1A-associated neurological disorder.