The dual PH domain protein Opy1 functions as a sensor and modulator of PtdIns(4,5)P₂ synthesis.

The EMBO Journal
Yading LingScott D Emr

Abstract

Phosphatidylinositol-4,5-bisphosphate, PtdIns(4,5)P(2), is an essential signalling lipid that regulates key processes such as endocytosis, exocytosis, actin cytoskeletal organization and calcium signalling. Maintaining proper levels of PtdIns(4,5)P(2) at the plasma membrane (PM) is crucial for cell survival and growth. We show that the conserved PtdIns(4)P 5-kinase, Mss4, forms dynamic, oligomeric structures at the PM that we term PIK patches. The dynamic assembly and disassembly of Mss4 PIK patches may provide a mechanism to precisely modulate Mss4 kinase activity, as needed, for localized regulation of PtdIns(4,5)P(2) synthesis. Furthermore, we identify a tandem PH domain-containing protein, Opy1, as a novel Mss4-interacting protein that partially colocalizes with PIK patches. Based upon genetic, cell biological, and biochemical data, we propose that Opy1 functions as a coincidence detector of the Mss4 PtdIns(4)P 5-kinase and PtdIns(4,5)P(2) and serves as a negative regulator of PtdIns(4,5)P(2) synthesis at the PM. Our results also suggest that additional conserved tandem PH domain-containing proteins may play important roles in regulating phosphoinositide signalling.

References

Jan 1, 1985·Annual Review of Biochemistry·L E Hokin
Sep 13, 1994·Proceedings of the National Academy of Sciences of the United States of America·L YaoT Kawakami
May 27, 1993·Nature·R J HaslamB A Hemmings
Oct 11, 1996·The Journal of Biological Chemistry·C S AbramsS E Rittenhouse
Feb 21, 2002·Molecular Biology of the Cell·Christopher J StefanScott D Emr
Dec 10, 2002·Annual Review of Physiology·Helen L Yin, Paul A Janmey
Jan 1, 2005·Immunology Letters·Atef Allam, Aaron J Marshall
Oct 26, 2005·Biochemical Society Transactions·V Haucke
Dec 2, 2005·Nature·Rudy Behnia, Sean Munro
Feb 24, 2006·Nature·Tobias C WaltherPeter Walter
May 18, 2006·Biology of the Cell·Michael R Logan, Craig A Mandato
Aug 2, 2006·Proceedings of the National Academy of Sciences of the United States of America·Michael KraussVolker Haucke
Oct 13, 2006·Nature·Gilbert Di Paolo, Pietro De Camilli
Feb 10, 2007·The EMBO Journal·Akiko Nakano-KobayashiYasunori Kanaho
Jan 23, 2008·Traffic·Iwona I Smaczynska-de RooijKathryn R Ayscough
Jan 25, 2008·Nature Reviews. Molecular Cell Biology·Mark A Lemmon
Jul 23, 2008·The Journal of Cell Biology·Declan J JamesThomas F J Martin
Sep 12, 2008·The EMBO Journal·Mariella VicinanzaMaria Antonietta De Matteis
Dec 17, 2008·The Journal of Cell Biology·Dan BairdScott D Emr
Feb 3, 2009·Current Biology : CB·Steven M MarkusWei-Lih Lee
Jun 16, 2010·Proceedings of the National Academy of Sciences of the United States of America·Lindsay S GarrentonJeremy Thorner
Oct 19, 2010·Journal of Molecular Biology·Aurélie BertinEva Nogales

❮ Previous
Next ❯

Citations

Aug 9, 2017·The Journal of Cell Biology·Chloe E SniderKathleen L Gould
Oct 24, 2013·The Plant Journal : for Cell and Molecular Biology·Mathilde Laetitia Audrey SimonYvon Jaillais
Feb 7, 2015·Genetics·Bruce L GoodeBeverly Wendland
Jun 20, 2013·Journal of Cell Science·Isabelle GuillasRobert A Arkowitz
May 4, 2013·Journal of Cell Science·Till KleckerBenedikt Westermann

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.