An essential role for a protein and lipid kinase complex in secretory protein sorting

Herman, Paul K.; Stack, Jeffrey H.; Emr, Scott D.

doi:10.1016/0962-8924(92)90048-r

Cited by 87 publications

(49 citation statements)

References 40 publications

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“…Two possibilities for the abnormal vacuolar dynamics in mutant pollen can be entertained. First, protein targeting to vacuoles, where PtdIns(3)P has been shown to be essential (Herman et al, 1992;Schu et al, 1993), may be defective in the mutant. In yeast, protein transport to the vacuole depends on the Vam7 t-SNARE, and its targeting to the vacuole is dependent on PtdIns(3)P generation (Cheever et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

“…However, in plants, genes that encode class I or II PI3K are missing, and only the class III PI3K, which makes PtdIns(3)P from PtdIns, has been identified (Hong and Verma, 1994;Welters et al, 1994). The prototype for this type of enzyme, Vps34p, was first identified in Saccharomyces cerevisiae, in which it is required for the delivery of soluble proteins to the vacuole (Herman et al, 1992;Schu et al, 1993). Subsequently, a human homolog was identified, and Vps34p-related PI3Ks are now known to exist in a range of other eukaryotes, including Dictyostelium (Zhou et al, 1995), Drosophila (Linassier et al, 1997), and plants (Hong and Verma, 1994;Welters et al, 1994).…”

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confidence: 99%

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The Arabidopsis Phosphatidylinositol 3-Kinase Is Important for Pollen Development

et al. 2008

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Phosphatidylinositol 3-kinase has been reported to be important for normal plant growth. To characterize the role of the enzyme further, we attempted to isolate Arabidopsis (Arabidopsis thaliana) plants that do not express the gene, but we could not recover homozygous mutant plants. The progeny of VPS34/vps34 heterozygous plants, harboring a T-DNA insertion, showed a segregation ratio of 1:1:0 for wild-type, heterozygous, and homozygous mutant plants, indicating a gametophytic defect. Genetic transmission analysis showed that the abnormal segregation ratio was due to failure to transmit the mutant allele through the male gametophyte. Microscopic observation revealed that 2-fold higher proportions of pollen grains in heterozygous plants than wild-type plants were dead or showed reduced numbers of nuclei. Many mature pollen grains from the heterozygous plants contained large vacuoles even until the mature pollen stage, whereas pollen from wild-type plants contained many small vacuoles beginning from the vacuolated pollen stage, which indicated that vacuoles in many of the heterozygous mutant pollen did not undergo normal fission after the first mitotic division. Taken together, our results suggest that phosphatidylinositol 3-kinase is essential for vacuole reorganization and nuclear division during pollen development.

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Section: Discussionmentioning

confidence: 99%

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The Arabidopsis Phosphatidylinositol 3-Kinase Is Important for Pollen Development

et al. 2008

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“…The Vps34p-Vps15p kinase complex is an important regulator of protein sorting in eukaryotic cells (14,16). We are interested in understanding how this complex is assembled and how the respective kinase activities are regulated.…”

Section: Discussionmentioning

confidence: 99%

“…However, more recent work has also implicated these molecules in the regulation of membrane-trafficking events within the secretory pathway (13,14). This latter role for phosphoinositides was first suggested by the sequence similarity shared by Vps34p and PI 3-kinases (15,16). Subsequent studies have since shown that other phosphoinositides in addition to PtdIns 3-phosphate (PtdIns(3)P) play an important role in controlling secretory traffic (13).…”

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The C Terminus of the Vps34p Phosphoinositide 3-Kinase Is Necessary and Sufficient for the Interaction with the Vps15p Protein Kinase

Budovskaya¹,

Hama²,

DeWald³

et al. 2002

Journal of Biological Chemistry

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Vps34p is a phosphatidylinositol 3-kinase that is part of a membrane-associated complex with the Vps15p protein kinase. This kinase complex is required for the delivery of soluble proteins to the lysosomal/vacuolar compartment of eukaryotic cells. This study examined the Vps34p-Vps15p association and identified the domains within each protein that were important for this interaction. Using several different approaches, the interaction domain within Vps34p was mapped to a 28-amino acid element near its C terminus. This Vps34p motif was both necessary and sufficient for the interaction with Vps15p. Two-hybrid mapping experiments indicated that two separate regions of Vps15p were required for the association with Vps34p; they are the N-terminal protein kinase domain and a set of three tandem repeats of about 39 amino acids each. Neither domain alone was sufficient for the interaction. These Vps15p repeat elements are similar in sequence to the HEAT motifs that have been implicated in protein interactions in other proteins, including the Huntingtin protein. Finally, these studies identified a novel motif at the very C terminus of Vps34p that was required for phosphatidylinositol 3-kinase activity. This domain is highly conserved specifically in all Vps34p-like phosphatidylinositol 3-kinases but is not required for the interaction with Vps15p. This study thus represents a first step toward a better understanding of how this Vps15p⅐Vps34p kinase complex is assembled and regulated in vivo.

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“…Initially, studies using the yeast Saccharomyces cerevisiae (5) demonstrated that the VPS34 gene encodes a phosphatidylinositol (PtdIns) 3-kinase that is required for protein transport from the late Golgi apparatus to the vacuole (2,6). In mammalian cells multiple isoforms of PtdIns 3-kinases mediate signal transduction events (7), and based on their differential sensitivity to the drug wortmannin, PtdIns 3-and 4-kinases were subsequently implicated in protein trafficking to lysosomes (8 -10).…”

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confidence: 99%

Inhibition of Phosphatidic Acid Synthesis Alters the Structure of the Golgi Apparatus and Inhibits Secretion in Endocrine Cells

Siddhanta¹,

Backer²,

Shields³

2000

Journal of Biological Chemistry

109

107

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In mammalian cells, activation of a Golgi-associated phospholipase D by ADP-ribosylation factor results in the hydrolysis of phosphatidylcholine to form phosphatidic acid (PA). This reaction stimulates the release of nascent secretory vesicles from the trans-Golgi network of endocrine cells. To understand the role of PA in mediating secretion, we have exploited the transphosphatidylation activity of phospholipase D. Rat anterior pituitary GH3 cells, which secrete growth hormone and prolactin, were treated with 1-butanol resulting in the synthesis of phosphatidylbutanol rather than PA. Under these conditions transport from the ER through the Golgi apparatus and secretion of polypeptide hormones were inhibited quantitatively. Furthermore, the in vitro synthesis of phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P 2 ) by Golgi membranes was inhibited quantitatively. Most significantly, in the presence of 1-butanol the architecture of the Golgi apparatus was disrupted, resulting in its disassembly and fragmentation. Removal of the alcohol resulted in the rapid restoration of Golgi structure and secretion of growth hormone and prolactin. Our results suggest that PA stimulation of PtdIns(4,5)P 2 synthesis is required for maintaining the structural integrity and function of the Golgi apparatus.

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An essential role for a protein and lipid kinase complex in secretory protein sorting

Cited by 87 publications

References 40 publications

The Arabidopsis Phosphatidylinositol 3-Kinase Is Important for Pollen Development

The Arabidopsis Phosphatidylinositol 3-Kinase Is Important for Pollen Development

The C Terminus of the Vps34p Phosphoinositide 3-Kinase Is Necessary and Sufficient for the Interaction with the Vps15p Protein Kinase

Inhibition of Phosphatidic Acid Synthesis Alters the Structure of the Golgi Apparatus and Inhibits Secretion in Endocrine Cells

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