Genetic Analysis of Yeast Yip1p Function Reveals a Requirement for Golgi-Localized Rab Proteins and Rab-Guanine Nucleotide Dissociation Inhibitor

By Chen, Catherine Z.; Calero, Monica et al. | Genetics, December 2004 | Go to article overview

Genetic Analysis of Yeast Yip1p Function Reveals a Requirement for Golgi-Localized Rab Proteins and Rab-Guanine Nucleotide Dissociation Inhibitor


Chen, Catherine Z., Calero, Monica, DeRegis, Carol J., Heidtman, Matthew, et al., Genetics


ABSTRACT

Yip1p is the first identified Rab-interacting membrane protein and the founder member of the YIP1 family, with both orthologs and paralogs found in all eukaryotic genomes. The exact role of Yip1p is unclear; YIP1 is an essential gene and defective alleles severely disrupt membrane transport and inhibit ER vesicle budding. Yip1p has the ability to physically interact with Rab proteins and the nature of this interaction has led to suggestions that Yip1p may function in the process by which Rab proteins translocate between cytosol and membranes. In this study we have investigated the physiological requirements for Yip1p action. Yip1p function requires Rab-GDI and Rab proteins, and several mutations that abrogate Yip1p function lack Rab-interacting capability. We have previously shown that Yip1p in detergent extracts has the capability to physically interact with Rab proteins in a promiscuous manner; however, a genetic analysis that covers every yeast Rab reveals that the Rab requirement in vivo is exclusively confined to a subset of Rab proteins that are localized to the Golgi apparatus.

RAS superfamily members have proven to be critical players in a variety of fundamental cellular processes, which they influence by modulation of their GTP binding and hydrolysis cycle. These small GTPases are commonly found to cycle between a cytosolic pool and a membrane-associated pool where the activated GTPases recruit their downstream effectors. The highly hydrophobic geranylgeranyl groups of Rho and Rab GTPases render them energetically unfavorable to partition into the cytosol as individual monomers. Cytosolic Rho and Rab proteins exist in a high-affinity dimeric complex with guanine nucleotide dissociation inhibitor (GDI) proteins (OLOFSSON 1999; ALORY and BALCH 2001). These GDI.GTPase complexes represent an inactive cytosolic reservoir of the GTPase and GDI must be induced to release its GTPase at a membrane site to enable cells to draw upon this reservoir. Mechanisms that promote GDI displacement and help recruit GTPases onto membranes are of great importance because such mechanisms will determine where and when the GTPases are activated. Possible candidates for a role in Rab protein membrane recruitment include the Rab-interacting YIP1 family of membrane proteins. Certainly the YIP1 family possess features that suggest a capability for participation in Rab membrane recruitment; they are capable of biochemical interaction with a variety of Rab proteins in a manner dependent on COOH-terminal prenylation (CALERO et al. 2002) and so might compete with Rab-GDI for Rab protein interactions in vivo.

YIP1 is an essential gene in Saccharomyces cerevsiae and extremely well conserved in evolution; the human ortholog can fully replace loss of the yeast gene (CALERO et al. 2003). In cellular lysates, Yip1p is capable of promiscuous interaction with Rab proteins, with a specific requirement for the double prenylation motif contained at the COOH termini that is one of the defining features of the Rab protein family. Recent studies combining in vitro reconstitution and cell biological and genetic analyses have demonstrated that Yip1p functions at an early stage in ER vesicle budding (BARROWMAN et al. 2003; HEIDTMAN et al. 2003). This function of Yip1p is difficult to reconcile with its connection to Rab proteins. Although Rab proteins are required for vesicle budding and cargo selection in several systems, it is possible to form fusion-competent transport vesicles from the ER in the absence of Ypt1p function, the Rab protein thought to regulate this particular transport step in vivo (CAO and BARLOWE 2000). Moreover, it is not known if Yip1p action in vivo requires Rab proteins, leaving open to question the apparent significance of the biochemical interactions observed between these proteins.

In this study we sought to further understand the two aspects of Yip1p function and determine if the interaction of Yip1p with Rab proteins is biologically significant. …

The rest of this article is only available to active members of Questia

Already a member? Log in now.

Notes for this article

Add a new note
If you are trying to select text to create highlights or citations, remember that you must now click or tap on the first word, and then click or tap on the last word.
One moment ...
Default project is now your active project.
Project items
Notes
Cite this article

Cited article

Style
Citations are available only to our active members.
Buy instant access to cite pages or passages in MLA 8, MLA 7, APA and Chicago citation styles.

(Einhorn, 1992, p. 25)

(Einhorn 25)

(Einhorn 25)

1. Lois J. Einhorn, Abraham Lincoln, the Orator: Penetrating the Lincoln Legend (Westport, CT: Greenwood Press, 1992), 25, http://www.questia.com/read/27419298.

Note: primary sources have slightly different requirements for citation. Please see these guidelines for more information.

Cited article

Genetic Analysis of Yeast Yip1p Function Reveals a Requirement for Golgi-Localized Rab Proteins and Rab-Guanine Nucleotide Dissociation Inhibitor
Settings

Settings

Typeface
Text size Smaller Larger Reset View mode
Search within

Search within this article

Look up

Look up a word

  • Dictionary
  • Thesaurus
Please submit a word or phrase above.
Print this page

Print this page

Why can't I print more than one page at a time?

Help
Full screen
Items saved from this article
  • Highlights & Notes
  • Citations
Some of your highlights are legacy items.

Highlights saved before July 30, 2012 will not be displayed on their respective source pages.

You can easily re-create the highlights by opening the book page or article, selecting the text, and clicking “Highlight.”

matching results for page

    Questia reader help

    How to highlight and cite specific passages

    1. Click or tap the first word you want to select.
    2. Click or tap the last word you want to select, and you’ll see everything in between get selected.
    3. You’ll then get a menu of options like creating a highlight or a citation from that passage of text.

    OK, got it!

    Cited passage

    Style
    Citations are available only to our active members.
    Buy instant access to cite pages or passages in MLA 8, MLA 7, APA and Chicago citation styles.

    "Portraying himself as an honest, ordinary person helped Lincoln identify with his audiences." (Einhorn, 1992, p. 25).

    "Portraying himself as an honest, ordinary person helped Lincoln identify with his audiences." (Einhorn 25)

    "Portraying himself as an honest, ordinary person helped Lincoln identify with his audiences." (Einhorn 25)

    "Portraying himself as an honest, ordinary person helped Lincoln identify with his audiences."1

    1. Lois J. Einhorn, Abraham Lincoln, the Orator: Penetrating the Lincoln Legend (Westport, CT: Greenwood Press, 1992), 25, http://www.questia.com/read/27419298.

    Cited passage

    Thanks for trying Questia!

    Please continue trying out our research tools, but please note, full functionality is available only to our active members.

    Your work will be lost once you leave this Web page.

    Buy instant access to save your work.

    Already a member? Log in now.

    Search by... Author
    Show... All Results Primary Sources Peer-reviewed

    Oops!

    An unknown error has occurred. Please click the button below to reload the page. If the problem persists, please try again in a little while.