Function of CSNK2/CK2 selectively affects the endoplasmic reticulum and the Golgi apparatus in mtor-mediated

Pablo Sanz-Martinez1,2, Rayene Berkane1,2, Alexandra Stolz1,2

  • 1Institute of Biochemistry 2 (IBC2), Goethe University, Frankfurt am Main, Germany.

Autophagy
|August 23, 2024
PubMed

Insights

Selective autophagy, or ER-phagy, maintains endoplasmic reticulum (ER) homeostasis. CSNK2 inhibition impacts ER-phagy, while ATR inhibition affects multiple organelle autophagy pathways.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Autophagy Research

Background:

  • Selective autophagy, including reticulophagy/ER-phagy, is crucial for endoplasmic reticulum (ER) homeostasis.
  • Autophagy receptors like RETREG/FAM134 are regulated by phosphorylation-dependent ubiquitination.
  • Kinases downstream of MTOR, such as ATR and CSNK2/CK2, influence reticulophagy flux.

Purpose of the Study:

  • To investigate the global proteomics changes upon inhibition of CSNK2 and ATR.
  • To elucidate the specific roles of CSNK2 and ATR in selective autophagy pathways.

Main Methods:

  • Global proteomics analysis.
  • Inhibition of CSNK2 using SGC-CK2-1.
  • Inhibition of ATR using VE-822.
  • Analysis of regulatory ubiquitination and receptor clustering.

Main Results:

  • CSNK2 inhibition prevented regulatory ubiquitination of RETREG1 and RETREG3, and formation of RETREG clusters.
  • CSNK2 inhibition's effects were primarily limited to ER/reticulophagy and Golgi/Golgiphagy.
  • ATR inhibition (ATRi) broadly impacted most organelle/selective autophagy pathways.

Conclusions:

  • CSNK2 plays a specific role in ER/reticulophagy and Golgi/Golgiphagy regulation.
  • ATR has a more widespread role, affecting the majority of selective autophagy pathways.
  • These findings provide resource data for understanding kinase regulation of selective autophagy.

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...
3.4K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

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...
3.8K
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,...
5.1K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

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...
5.3K
Autophagy01:27

Autophagy

Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
4.2K
M-Cdk Drives Transition Into Mitosis02:15

M-Cdk Drives Transition Into Mitosis

Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
5.5K