Limits...
Assembly of the PtdIns 4-kinase Stt4 complex at the plasma membrane requires Ypp1 and Efr3.

Baird D, Stefan C, Audhya A, Weys S, Emr SD - J. Cell Biol. (2008)

Bottom Line: We identify the membrane protein Efr3 as an additional component of Stt4 PIK patches.Efr3 is essential for assembly of both Ypp1 and Stt4 at PIK patches.We conclude that Ypp1 and Efr3 are required for the formation and architecture of Stt4 PIK patches and ultimately PM-based PtdIns4P signaling.

View Article: PubMed Central - PubMed

Affiliation: Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853, USA.

ABSTRACT
The phosphoinositide phosphatidylinositol 4-phosphate (PtdIns4P) is an essential signaling lipid that regulates secretion and polarization of the actin cytoskeleton. In Saccharomyces cerevisiae, the PtdIns 4-kinase Stt4 catalyzes the synthesis of PtdIns4P at the plasma membrane (PM). In this paper, we identify and characterize two novel regulatory components of the Stt4 kinase complex, Ypp1 and Efr3. The essential gene YPP1 encodes a conserved protein that colocalizes with Stt4 at cortical punctate structures and regulates the stability of this lipid kinase. Accordingly, Ypp1 interacts with distinct regions on Stt4 that are necessary for the assembly and recruitment of multiple copies of the kinase into phosphoinositide kinase (PIK) patches. We identify the membrane protein Efr3 as an additional component of Stt4 PIK patches. Efr3 is essential for assembly of both Ypp1 and Stt4 at PIK patches. We conclude that Ypp1 and Efr3 are required for the formation and architecture of Stt4 PIK patches and ultimately PM-based PtdIns4P signaling.

Show MeSH
Organization of Stt4 PIK patches at the PM. Ypp1 is a multivalent linker of Stt4 molecules ensuring the stability of the lipid kinase and the organization of the PIK patch. Efr3 anchors the Stt4–Ypp1 complex at the PM by binding Ypp1. TMD, transmembrane domain; LKUD, lipid kinase unique domain; PI4K, PtdIns 4-kinase domain.
© Copyright Policy
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC2600738&req=5

fig9: Organization of Stt4 PIK patches at the PM. Ypp1 is a multivalent linker of Stt4 molecules ensuring the stability of the lipid kinase and the organization of the PIK patch. Efr3 anchors the Stt4–Ypp1 complex at the PM by binding Ypp1. TMD, transmembrane domain; LKUD, lipid kinase unique domain; PI4K, PtdIns 4-kinase domain.

Mentions: Fig. 9 provides a model that illustrates how we propose the Stt4 PIK patch organizes at the PM. First, Ypp1 is capable of interacting with at least two separate regions within the N terminus of Stt4 (Fig. 2 D). As a result, Ypp1 could act as a multivalent linker to organize/cluster multiple (∼25–30) Stt4 proteins into a PIK patch. Stt4–Ypp1 complexes localize to the PM and further assemble through Efr3 to direct Stt4-mediated PtdIns4P production at the PM. Additional components, such as Sfk1 (Audhya and Emr, 2002), may contribute to the organization and activation of this complex. Because there are potentially other factors associated with regulation of this complex, our future work will be directed toward identifying these components and determining how each factor mediates PIK patch dynamics and PtdIns4P metabolism.


Assembly of the PtdIns 4-kinase Stt4 complex at the plasma membrane requires Ypp1 and Efr3.

Baird D, Stefan C, Audhya A, Weys S, Emr SD - J. Cell Biol. (2008)

Organization of Stt4 PIK patches at the PM. Ypp1 is a multivalent linker of Stt4 molecules ensuring the stability of the lipid kinase and the organization of the PIK patch. Efr3 anchors the Stt4–Ypp1 complex at the PM by binding Ypp1. TMD, transmembrane domain; LKUD, lipid kinase unique domain; PI4K, PtdIns 4-kinase domain.
© Copyright Policy
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC2600738&req=5

fig9: Organization of Stt4 PIK patches at the PM. Ypp1 is a multivalent linker of Stt4 molecules ensuring the stability of the lipid kinase and the organization of the PIK patch. Efr3 anchors the Stt4–Ypp1 complex at the PM by binding Ypp1. TMD, transmembrane domain; LKUD, lipid kinase unique domain; PI4K, PtdIns 4-kinase domain.
Mentions: Fig. 9 provides a model that illustrates how we propose the Stt4 PIK patch organizes at the PM. First, Ypp1 is capable of interacting with at least two separate regions within the N terminus of Stt4 (Fig. 2 D). As a result, Ypp1 could act as a multivalent linker to organize/cluster multiple (∼25–30) Stt4 proteins into a PIK patch. Stt4–Ypp1 complexes localize to the PM and further assemble through Efr3 to direct Stt4-mediated PtdIns4P production at the PM. Additional components, such as Sfk1 (Audhya and Emr, 2002), may contribute to the organization and activation of this complex. Because there are potentially other factors associated with regulation of this complex, our future work will be directed toward identifying these components and determining how each factor mediates PIK patch dynamics and PtdIns4P metabolism.

Bottom Line: We identify the membrane protein Efr3 as an additional component of Stt4 PIK patches.Efr3 is essential for assembly of both Ypp1 and Stt4 at PIK patches.We conclude that Ypp1 and Efr3 are required for the formation and architecture of Stt4 PIK patches and ultimately PM-based PtdIns4P signaling.

View Article: PubMed Central - PubMed

Affiliation: Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY 14853, USA.

ABSTRACT
The phosphoinositide phosphatidylinositol 4-phosphate (PtdIns4P) is an essential signaling lipid that regulates secretion and polarization of the actin cytoskeleton. In Saccharomyces cerevisiae, the PtdIns 4-kinase Stt4 catalyzes the synthesis of PtdIns4P at the plasma membrane (PM). In this paper, we identify and characterize two novel regulatory components of the Stt4 kinase complex, Ypp1 and Efr3. The essential gene YPP1 encodes a conserved protein that colocalizes with Stt4 at cortical punctate structures and regulates the stability of this lipid kinase. Accordingly, Ypp1 interacts with distinct regions on Stt4 that are necessary for the assembly and recruitment of multiple copies of the kinase into phosphoinositide kinase (PIK) patches. We identify the membrane protein Efr3 as an additional component of Stt4 PIK patches. Efr3 is essential for assembly of both Ypp1 and Stt4 at PIK patches. We conclude that Ypp1 and Efr3 are required for the formation and architecture of Stt4 PIK patches and ultimately PM-based PtdIns4P signaling.

Show MeSH