Related Experiment Video

Updated: Aug 30, 2025

Oligopeptide Competition Assay for Phosphorylation Site Determination
09:16

Oligopeptide Competition Assay for Phosphorylation Site Determination

Published on: May 18, 2017

8.5K

Phosphorylation of FAM134C by CK2 controls starvation-induced ER-phagy

Giorgia Di Lorenzo1, Francescopaolo Iavarone1, Marianna Maddaluno1

  • 1Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy.

Science Advances
|August 31, 2022
PubMed

Insights

FAM134C protein regulates endoplasmic reticulum degradation (ER-phagy) through phosphorylation. Starvation activates FAM134C by reducing this phosphorylation, impacting liver lipid metabolism.

Area of Science:

  • Cellular Biology
  • Autophagy Research
  • Molecular Mechanisms

Background:

  • Selective degradation of the endoplasmic reticulum (ER) via autophagy (ER-phagy) is crucial for cellular homeostasis.
  • ER-phagy receptors, like FAM134 proteins, initiate this process by linking ER fragments to autophagosomes.
  • FAM134A, FAM134B, and FAM134C are known ER-phagy receptors, but their differential regulation remains unclear.

Purpose of the Study:

  • To investigate the differential regulation of FAM134C, an ER-phagy receptor, during starvation.
  • To elucidate the specific activation mechanism of FAM134C and its role in liver lipid metabolism.

Main Methods:

  • Utilized casein kinase 2 (CK2) and mTORC1 inhibition studies to examine FAM134C phosphorylation.
  • Employed a novel in vivo tool for ER-phagy studies.
  • Generated and analyzed FAM134C knockout mice.

Main Results:

  • FAM134C is phosphorylated by CK2 in fed conditions, inhibiting its binding to LC3 and thus ER-phagy.
  • Starvation leads to mTORC1 inhibition, reducing FAM134C phosphorylation and activating ER-phagy.
  • FAM134C phosphorylation is physiologically relevant for starvation-induced ER-phagy in liver lipid metabolism.

Conclusions:

  • A unique activation mechanism for FAM134C during starvation involves the regulation of CK2-mediated phosphorylation.
  • This mechanism highlights autophagy selectivity during starvation and provides insight into ER-phagy regulation.
  • FAM134C plays a significant role in liver lipid metabolism through starvation-induced ER-phagy.

More Related Videos

Exploring the Regulation of Lipid Droplet Catabolism through Lipophagy07:20

Exploring the Regulation of Lipid Droplet Catabolism through Lipophagy

Published on: January 31, 2025

630
Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay12:26

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay

Published on: May 3, 2018

18.8K

Related Concept Videos

PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

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...
3.9K
Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

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,...
5.2K
Phosphorylation01:02

Phosphorylation

The addition or removal of phosphate groups from proteins is the most common chemical modification that regulates cellular processes. These modifications can affect the structure, activity, stability, and localization of proteins within cells as well as their interactions with other proteins.
During phosphorylation, protein kinases transfer the terminal phosphate group of ATP to specific amino acid side chains of substrate proteins. Serine, threonine, and tyrosine are the most commonly...
50.9K
Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
13.3K
Stringent Response in E. coli01:23

Stringent Response in E. coli

Bacterial growth is closely tied to nutrient availability, with cells proliferating exponentially under favorable conditions and entering a stationary phase when resources become scarce. This transition is mediated by a regulatory mechanism known as the stringent response, which allows bacteria to adapt to nutrient deprivation by modulating gene expression and metabolic activity.During nutrient scarcity, intracellular amino acid levels decline. It results in the accumulation of uncharged tRNAs...
45
cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
6.5K