AGAP1, an Endosome-associated, Phosphoinositide-dependent ADP-ribosylation Factor GTPase-activating Protein That Affects Actin Cytoskeleton

Nie, Zhongzhen; Stanley, Katherine T.; Stauffer, Stacey; Jacques, Kerry M.; Hirsch, Dianne S.; Takei, Jiro; Randazzo, Paul A.

doi:10.1074/jbc.m202969200

Cited by 119 publications

(123 citation statements)

References 45 publications

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“…8C; Koizumi et al, 2005). The partial localization of AGD1 to FM4-64-labeled bodies that we observed here is consistent with the endosomal localization of the closely related animal AZAPs (Jackson et al, 2000;Nie et al, 2002). The differences in localization, domain organization, and possibly ARF substrate preference between AGD1 and AGD10 could likely explain the different nature of tip growth defects caused by their respective mutants.…”

Section: Discussionsupporting

confidence: 73%

“…In animal cells, AZAP-type ARF-GAPs, by virtue of their effects on membrane trafficking, induce a remodeling of the actin cytoskeleton (Nie et al, 2002;Randazzo and Hirsch, 2004;Randazzo et al, 2007). Modification in membrane structure by AZAP has been shown to be mediated in part by the BAR domain at the N terminus of the protein (Nie et al, 2006) and has been proposed to facilitate the binding of other classes of small GTPases (Habermann, 2004).…”

Section: Discussionmentioning

confidence: 99%

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A Class I ADP-Ribosylation Factor GTPase-Activating Protein Is Critical for Maintaining Directional Root Hair Growth in Arabidopsis

et al. 2008

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Membrane trafficking and cytoskeletal dynamics are important cellular processes that drive tip growth in root hairs. These processes interact with a multitude of signaling pathways that allow for the efficient transfer of information to specify the direction in which tip growth occurs. Here, we show that AGD1, a class I ADP ribosylation factor GTPase-activating protein, is important for maintaining straight growth in Arabidopsis (Arabidopsis thaliana) root hairs, since mutations in the AGD1 gene resulted in wavy root hair growth. Live cell imaging of growing agd1 root hairs revealed bundles of endoplasmic microtubules and actin filaments extending into the extreme tip. The wavy phenotype and pattern of cytoskeletal distribution in root hairs of agd1 partially resembled that of mutants in an armadillo repeat-containing kinesin (ARK1). Root hairs of double agd1 ark1 mutants were more severely deformed compared with single mutants. Organelle trafficking as revealed by a fluorescent Golgi marker was slightly inhibited, and Golgi stacks frequently protruded into the extreme root hair apex of agd1 mutants. Transient expression of green fluorescent protein-AGD1 in tobacco (Nicotiana tabacum) epidermal cells labeled punctate bodies that partially colocalized with the endocytic marker FM4-64, while ARK1-yellow fluorescent protein associated with microtubules. Brefeldin A rescued the phenotype of agd1, indicating that the altered activity of an AGD1-dependent ADP ribosylation factor contributes to the defective growth, organelle trafficking, and cytoskeletal organization of agd1 root hairs. We propose that AGD1, a regulator of membrane trafficking, and ARK1, a microtubule motor, are components of converging signaling pathways that affect cytoskeletal organization to specify growth orientation in Arabidopsis root hairs.

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Section: Discussionsupporting

confidence: 73%

Section: Discussionmentioning

confidence: 99%

A Class I ADP-Ribosylation Factor GTPase-Activating Protein Is Critical for Maintaining Directional Root Hair Growth in Arabidopsis

et al. 2008

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“…The FG repeats in nucleoporins are believed to mediate protein-protein interactions, and in the case of hRIP, are required for its interaction with Rev in vivo. At its N terminus, hRIP contains a zinc finger motif (Krishna et al 2003), which shares a high degree of sequence identity with a subclass of C 4 H 2 -type zinc-finger domains found in proteins involved in vesicular trafficking, intracellular protein localization, cytoskeletal rearrangement, RNA metabolism, or signal transduction (Cukierman et al 1995;Kirchhausen 2000;Premont et al 2000;Turner et al 2001;Nie et al 2002;Dubois et al 2003). Within the central body of the protein are stretches of serine/threonine-rich sequences (S/TRR), several of which are substrates for a subset of cellular kinases, and thus, possible targets for regulation (Maraldi et al 1999;Parker and Parkinson 2001;Biondi and Nebreda 2003).…”

mentioning

confidence: 99%

hRIP, a cellular cofactor for Rev function, promotes release of HIV RNAs from the perinuclear region

Sánchez-Velar

Udofia²,

Yu³

et al. 2003

Genes Dev.

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Human immunodeficiency virus Rev facilitates the cytoplasmic accumulation of viral RNAs that contain aRev binding site. A human Rev-interacting protein (hRIP) was originally identified based on its ability to interact with the Rev nuclear export signal (NES) in yeast two-hybrid assays. To date, however, the function of hRIP and a role for hRIP in Rev-directed RNA export have remained elusive. Here we ablate hRIP activity with a dominant-negative mutant or RNA interference and analyze Rev function by RNA in situ hybridization. We find, unexpectedly, that in the absence of functional hRIP, Rev-directed RNAs mislocalize and aberrantly accumulate at the nuclear periphery, where hRIP is localized. In contrast, in the absence of Rev or the Rev cofactor CRM1, Rev-directed RNAs remain nuclear. We further show that the RNA mislocalization pattern resulting from loss of hRIP activity is highly specific to Rev function: the intracellular distribution of cellular poly(A) + mRNA, nuclear proteins, and, most important, NES-containing proteins, are unaffected. Thus, hRIP is an essential cellular Rev cofactor, which acts at a previously unanticipated step in HIV-1 RNA export: movement of RNAs from the nuclear periphery to the cytoplasm. Animal viruses often encode regulatory proteins, which facilitate expression of their viral genes in the host cell. One such example is the human immunodeficiency virus type 1 (HIV-1) Rev protein, which uses a novel mechanism to regulate viral messenger RNA (mRNA) export from the nucleus. Rev is a sequence-specific RNA binding protein that facilitates the cytoplasmic accumulation of the intron-containing HIV-1 gag-pol and env mRNAs (Cullen 2002). Rev interacts with a cis-acting viral RNA element in these mRNAs designated the Rev responsive element (RRE; Pollard and Malim 1998; Hope 1999). Rev contains two distinct functional domains: an arginine-rich RNA binding motif (ARM) and a leucinerich "effector" domain. Rev's ARM domain confers sequence-specific RNA binding, protein oligomerization, and nuclear targeting (Frankel and Young 1998). Rev's effector domain contains a leucine-rich nuclear export signal (NES), which binds the nuclear export receptor CRM1 (Weis 2002). Other cellular proteins have been shown to interact directly or indirectly with the Rev NES, including the kinesin-like Rev/Rex effector binding protein (REBP) and the eukaryotic initiation factor-5 alpha (eIF-5␣; Bevec et al. 1996;Dayton 1996;Kjems and Askjaer 2000;Venkatesh et al. 2003).The human Rev-interacting protein (hRIP), also known as hRab or Hrb, was identified using a yeast twohybrid screen with Rev as the bait (Bogerd et al. 1995;Fritz et al. 1995). Additional studies demonstrated a strong correlation between the ability of Rev NES mutants to support Rev function in yeast and their ability to interact with hRIP in the two-hybrid assay (Stutz et al. 1996). However, subsequent genetic analyses indicate the Rev-hRIP interaction is indirect, and is likely bridged by CRM1 (Fritz and Green 1996;Henderson and Percipalle 1997;Ne...

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“…For instance, phosphatidylinositols bind the PH domain of dynamin and activate its GTPase activity, which is important in dynamin function during vesicle budding (6). Phosphoinositides can convert Arf-GTP into Arf-GDP by binding to PH domain of centaurin ␤ family of Arf-GAPs, including ASAP1 and 2 (7)(8)(9). PIKE-A contains a PH domain, which separates the N-terminal GTPase and C-terminal Arf-GAP domains.…”

mentioning

confidence: 99%

Phosphoinositol lipids bind to phosphatidylinositol 3 (PI3)-kinase enhancer GTPase and mediate its stimulatory effect on PI3-kinase and Akt signalings

Liu

2005

Proc. Natl. Acad. Sci. U.S.A.

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Phosphatidylinositol 3 (PI3)-kinase enhancer (PIKE) is a nuclearGTPase that enhances PI3-kinase activity in a GTP-dependent manner. Both PIKE-L and -A isoforms contain GTPase, pleckstrin homology (PH), ADP ribosylation factor-GTPase-activating protein, and two ankyrin repeats domains, and C-terminal ADP ribosylation factor-GTPase-activating protein activates its internal GTPase activity. However, whether PH domain modulates the intramolecular action and subsequently influences its downstream signalings remains elusive. Here we show that PH domain from PIKE-L robustly binds PI(3,4,5)P3 and exclusively resides in the nucleus. By contrast, the mutant (K679,687N), unable to bind phosphoinositol lipids, translocates to the cytoplasm. This mutation substantially compromises the stimulatory effects on PI3-kinase by PIKE-L. Surprisingly, PH domain from PIKE-A distributes in the cytoplasm. Similar mutation in PH domain of PIKE-A abolishes its binding to PI(3,4,5)P3 and significantly decreases its activation of Akt. Moreover, amplified PIKE-A from human cancers contains mutations and highly stimulates Akt kinase activity, correlating with its GTPase activity. Thus, phosphatidylinositols regulate PIKE GTPase activity, mediating its downstream PI3-kinase͞Akt signaling through a feedback mechanism by binding to its PH domain.pleckstrin homology domain ͉ nuclear translocation ͉ negative feedback ͉ GTPase activation P hosphatidylinositol 3 (PI3)-kinase enhancer (PIKE) is a recently identified brain-specific nuclear GTPase that binds PI3-kinase and stimulates its lipid kinase activity. PIKE activates nuclear PI3-kinase in a GTP-dependent manner (1). Nerve growth factor elicits membrane-associated 4.1N nuclear translocation and interaction with PIKE, which was initially identified as a 4.1N-binding partner in a yeast two-hybrid screening. The binding of 4.1N to PIKE prevents its interactions with nuclear PI3-kinase, leading to inactivation of nuclear PI3-kinase. To date, three forms of PIKE have been characterized, PIKE-S, PIKE-L, and PIKE-A. PIKE-S is the initially identified shorter isoform (1). PIKE-L, a longer isoform of PIKE gene, differs from PIKE-S by C-terminal extension containing ADP ribosylation factor-GTPase activating protein (Arf-GAP) and two ankyrin repeats domains. In contrast to the exclusive nuclear localization of PIKE-S, PIKE-L occurs in both the nucleus and the cytoplasm (2). In addition, we show that WT merlin, binds PIKE-L and inhibits PI3-kinase activity. This suppression of PI3-kinase activity results from merlin disrupting the binding of PIKE-L to PI3-kinase (3). Recently, a third PIKE isoform, PIKE-A, was identified in human glioblastoma multiforme brain cancers. We have reported that PIKE-A is coamplified with cyclin-dependent kinase 4 in a variety of human cancers. Unlike the brain-specific PIKE-L and -S isoforms, PIKE-A distributes in various tissues. PIKE-A contains the same domains present in PIKE-L but lacks N-terminal proline-rich domain, which binds PI3-kinase and PLC-␥1. Instead, PIKE-A specif...

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AGAP1, an Endosome-associated, Phosphoinositide-dependent ADP-ribosylation Factor GTPase-activating Protein That Affects Actin Cytoskeleton

Cited by 119 publications

References 45 publications

A Class I ADP-Ribosylation Factor GTPase-Activating Protein Is Critical for Maintaining Directional Root Hair Growth in Arabidopsis

A Class I ADP-Ribosylation Factor GTPase-Activating Protein Is Critical for Maintaining Directional Root Hair Growth in Arabidopsis

hRIP, a cellular cofactor for Rev function, promotes release of HIV RNAs from the perinuclear region

Phosphoinositol lipids bind to phosphatidylinositol 3 (PI3)-kinase enhancer GTPase and mediate its stimulatory effect on PI3-kinase and Akt signalings

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