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

Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

2.8K
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
2.8K
Catenins01:23

Catenins

2.2K
Catenins are characterized by multiple binding domains and dynamic structures that allow them to function as linker proteins in cell junction complexes. All catenins, except α-catenin, contain a characteristic protein sequence called the armadillo repeat and are therefore also called armadillo proteins.
Catenins in Cell Junctions
Catenins bind to cell adhesion molecules such as cadherins and link them to different cytoskeletal proteins depending on the type of cell junction. At the...
2.2K
Cell Motility through Blebbing01:16

Cell Motility through Blebbing

1.9K
Blebs are a type of membrane protrusion formed by the internal hydrostatic pressure of the cytoplasm. Blebs are observed in several cell types, including fibroblasts, immune cells, and single-celled organisms like the amoeba. The primary function of blebs is cell locomotion and apoptosis, but they are also found during necrosis and cell division. The life cycle of a bleb comprises an initiation phase followed by the expansion and retraction phases.
Blebbing Through the Matrix
In multicellular...
1.9K
Notch Signaling Pathway03:14

Notch Signaling Pathway

4.6K
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
4.6K
Cell Adhesion Molecules - Types and Functions01:20

Cell Adhesion Molecules - Types and Functions

8.1K
Cell adhesion molecules (CAMs) are pivotal to multicellularity and the coordinated functioning of tissues and organ systems. They enable physical interactions between cells and provide mechanical strength to tissues. They also function as receptors for signal transmission across the plasma membrane. The CAMs are broadly classified into four families - integrins, cadherins, selectins, and immunoglobulin-like CAMs (IgCAMs).
CAM Families
The Integrin family of proteins is primarily  involved...
8.1K
Cell Adhesion Molecules - Types and Functions01:20

Cell Adhesion Molecules - Types and Functions

4.2K
4.2K

You might also read

Related Articles

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

Sort by
Same author

Metabolomic profile of barnyard millet (<i>Echinochloa Esculenta</i>) and its application in white carrot-based dairy product (kheer) preparation.

Food chemistry: X·2026
Same author

Engineering Brain Injury In Vitro: Human iPSC-Based Organoids in Microfluidic Systems.

Applied sciences (Basel, Switzerland)·2026
Same author

iS2C2: a cointelligent platform for mechanistic discovery of disease cellular crosstalk.

Signal transduction and targeted therapy·2026
Same author

Recapitulation of plaque formation, tau pathology, and neurodegeneration in a human 3D matrix model of Alzheimer's disease.

Cell reports methods·2026
Same author

Innate Immune Evasion of Lyme Disease Pathogen Drives Alzheimer-Like Pathology.

Research square·2026
Same author

Ready to reconstitute foxtail millet pudding mix: Preparation and characterization for structural, morphological, physico-chemical, textural and sensory attributes.

Food science and technology international = Ciencia y tecnologia de los alimentos internacional·2026

Related Experiment Video

Updated: May 4, 2026

Bead Aggregation Assays for the Characterization of Putative Cell Adhesion Molecules
08:15

Bead Aggregation Assays for the Characterization of Putative Cell Adhesion Molecules

Published on: October 17, 2014

9.5K

BACE1 activity regulates cell surface contactin-2 levels.

Vivek Gautam, Carla D'Avanzo, Matthias Hebisch

  • 1Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. dora_kovacs@hms.harvard.edu.

Molecular Neurodegeneration
|January 11, 2014
PubMed
Summary

Beta-secretase 1 (BACE1) cleaves contactin-2, regulating its surface levels in neurons. This finding is crucial for understanding Alzheimer's disease (AD) and BACE1 inhibition side effects.

More Related Videos

Analyzing Cell Surface Adhesion Remodeling in Response to Mechanical Tension Using Magnetic Beads
07:55

Analyzing Cell Surface Adhesion Remodeling in Response to Mechanical Tension Using Magnetic Beads

Published on: March 8, 2017

8.0K
Horizontal Gel Electrophoresis for Enhanced Detection of Protein-RNA Complexes
06:36

Horizontal Gel Electrophoresis for Enhanced Detection of Protein-RNA Complexes

Published on: July 28, 2017

11.2K

Related Experiment Videos

Last Updated: May 4, 2026

Bead Aggregation Assays for the Characterization of Putative Cell Adhesion Molecules
08:15

Bead Aggregation Assays for the Characterization of Putative Cell Adhesion Molecules

Published on: October 17, 2014

9.5K
Analyzing Cell Surface Adhesion Remodeling in Response to Mechanical Tension Using Magnetic Beads
07:55

Analyzing Cell Surface Adhesion Remodeling in Response to Mechanical Tension Using Magnetic Beads

Published on: March 8, 2017

8.0K
Horizontal Gel Electrophoresis for Enhanced Detection of Protein-RNA Complexes
06:36

Horizontal Gel Electrophoresis for Enhanced Detection of Protein-RNA Complexes

Published on: July 28, 2017

11.2K

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Biochemistry

Background:

  • Beta-secretase 1 (BACE1) is a key therapeutic target for Alzheimer's disease (AD).
  • Potential side effects of BACE1 inhibition are not fully understood due to uncharacterized substrate cleavages.
  • BACE1's role in cleaving over 60 substrates, including contactin-2, requires further investigation.

Purpose of the Study:

  • To investigate the BACE1-mediated cleavage of human contactin-2.
  • To determine the impact of BACE1 activity on contactin-2 surface levels and release.
  • To explore the physiological relevance of BACE1-contactin-2 interaction in neuronal cells.

Main Methods:

  • Protein sequence analysis to identify putative BACE1 cleavage sites on contactin-2.
  • Overexpression of BACE1 in CHO cells and primary neurons to assess contactin-2 release.
  • Pharmacological inhibition of BACE1 to evaluate its effect on soluble contactin-2 secretion.
  • Site-directed mutagenesis of the BACE1 cleavage site on contactin-2.
  • Immunofluorescence and surface-biotinylation assays to quantify cell surface contactin-2 levels.
  • Analysis of human Alzheimer's disease brain samples.

Main Results:

  • Contactin-2 possesses a strong putative BACE1 cleavage site near its GPI membrane linker.
  • BACE1 overexpression increased soluble contactin-2 release, while BACE1 inhibition decreased it.
  • Mutation of the BACE1 cleavage site significantly impaired soluble contactin-2 release.
  • BACE1 activity was shown to tightly regulate contactin-2 surface levels in both cell lines and primary neurons.
  • Contactin-2 levels were decreased in AD brain samples, inversely correlating with elevated BACE1 levels.

Conclusions:

  • Mouse and human contactin-2 are confirmed physiological substrates of BACE1.
  • BACE1-mediated cleavage of contactin-2 critically regulates its surface expression in neuronal cells.
  • BACE1's regulation of contactin-2 surface levels suggests a role in cell adhesion, neurite outgrowth, and axon guidance.