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

PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

4.0K
The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
4.0K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

3.9K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.9K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

6.1K
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
6.1K
GTPases and their Regulation02:14

GTPases and their Regulation

2.4K
2.4K
Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

5.3K
Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
5.3K
Assembly of Signaling Complexes01:30

Assembly of Signaling Complexes

5.9K
Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
5.9K

You might also read

Related Articles

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

Sort by
Same author

Structural Mechanism and Cellular Restriction of Tau Seeding from Endolysosomes.

bioRxiv : the preprint server for biology·2026
Same author

LASER couples damage sensing to ESCRT assembly for lysosome repair.

Nature·2026
Same author

Genome-wide classification of tumor-derived reads from bulk long-read sequencing.

bioRxiv : the preprint server for biology·2026
Same author

Metapipeline-DNA: A comprehensive germline and somatic genomics Nextflow pipeline.

Cell reports methods·2026
Same author

Reconstitution of multistep recruitment of ULK1 to membranes in autophagy.

bioRxiv : the preprint server for biology·2025
Same author

Structural basis for mTORC1 activation on the lysosomal membrane.

Nature·2025
Same journal

Publisher Correction: Interplay between cohesin and RNA polymerase II in regulating chromatin interactions and gene transcription.

Nature structural & molecular biology·2026
Same journal

An asymmetric non-canonical nucleosome shapes the directionality of transcription outcomes.

Nature structural & molecular biology·2026
Same journal

Structural insights into neurokinin 2 receptor selectivity hold implications for obesity therapeutics.

Nature structural & molecular biology·2026
Same journal

Genome-wide absolute quantification of chromatin looping.

Nature structural & molecular biology·2026
Same journal

Putting numbers on chromatin looping.

Nature structural & molecular biology·2026
Same journal

Transcriptional readthrough progresses from incidental byproduct to therapeutic opportunity.

Nature structural & molecular biology·2026
See all related articles

Related Experiment Video

Updated: Sep 13, 2025

Isolation of Primary Mouse Hepatocytes for Nascent Protein Synthesis Analysis by Non-radioactive L-azidohomoalanine Labeling Method
08:04

Isolation of Primary Mouse Hepatocytes for Nascent Protein Synthesis Analysis by Non-radioactive L-azidohomoalanine Labeling Method

Published on: October 23, 2018

19.1K

Structural basis for mTORC1 regulation by the CASTOR1-GATOR2 complex.

Rachel M Jansen1,2, Clément Maghe1,2, Karla Tapia1

  • 1Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.

Nature Structural & Molecular Biology
|July 27, 2025
PubMed
Summary
This summary is machine-generated.

The study reveals how the arginine sensor CASTOR1 interacts with the GATOR2 complex to regulate mTORC1 activation. This interaction is crucial for controlling cell metabolism in response to nutrient availability.

More Related Videos

Polysome Fractionation and Analysis of Mammalian Translatomes on a Genome-wide Scale
10:56

Polysome Fractionation and Analysis of Mammalian Translatomes on a Genome-wide Scale

Published on: May 17, 2014

68.9K
Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants
07:38

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

272

Related Experiment Videos

Last Updated: Sep 13, 2025

Isolation of Primary Mouse Hepatocytes for Nascent Protein Synthesis Analysis by Non-radioactive L-azidohomoalanine Labeling Method
08:04

Isolation of Primary Mouse Hepatocytes for Nascent Protein Synthesis Analysis by Non-radioactive L-azidohomoalanine Labeling Method

Published on: October 23, 2018

19.1K
Polysome Fractionation and Analysis of Mammalian Translatomes on a Genome-wide Scale
10:56

Polysome Fractionation and Analysis of Mammalian Translatomes on a Genome-wide Scale

Published on: May 17, 2014

68.9K
Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants
07:38

Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants

Published on: June 6, 2025

272

Area of Science:

  • Cellular metabolism
  • Molecular biology
  • Signal transduction

Background:

  • Mechanistic target of rapamycin complex 1 (mTORC1) regulates cell metabolism.
  • Amino acid availability controls mTORC1 via Rag GTPases at the lysosome.
  • GATOR1 inactivates mTORC1 under low nutrients, regulated by GATOR2 and amino acid sensors.

Purpose of the Study:

  • To elucidate the structural mechanism of arginine sensing by CASTOR1 and its interaction with GATOR2.
  • To understand how CASTOR1 binding to GATOR2 disinhibits GATOR1 under low arginine conditions.

Main Methods:

  • Cryo-electron microscopy (cryo-EM) structure determination of human GATOR2 bound to CASTOR1.
  • Biochemical analysis of protein-protein interactions and regulatory mechanisms.

Main Results:

  • The cryo-EM structure reveals two MIOS WD40 domains of GATOR2 engaging with a CASTOR1 homodimer.
  • CASTOR1's MIOS-binding interface, distal to the arginine pocket, interacts with GATOR2.
  • Arginine binding induces loop ordering in CASTOR1, blocking the MIOS-binding interface and disrupting GATOR2 interaction.

Conclusions:

  • The structural mechanism explains how arginine availability modulates CASTOR1-GATOR2 binding.
  • This regulation effectively communicates nutrient status to the mTORC1 pathway.
  • The findings provide insights into nutrient sensing and metabolic control at the molecular level.