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Dive into the research topics where Peter Mayinger is active.

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Featured researches published by Peter Mayinger.


Journal of Cell Biology | 2008

Integration of Golgi trafficking and growth factor signaling by the lipid phosphatase SAC1.

Anastasia Blagoveshchenskaya; Fei Ying Cheong; Holger M. Rohde; Greta Glover; Andreas Knödler; Teresa Nicolson; Guido Boehmelt; Peter Mayinger

When a growing cell expands, lipids and proteins must be delivered to its periphery. Although this phenomenon has been observed for decades, it remains unknown how the secretory pathway responds to growth signaling. We demonstrate that control of Golgi phosphatidylinositol-4-phosphate (PI(4)P) is required for growth-dependent secretion. The phosphoinositide phosphatase SAC1 accumulates at the Golgi in quiescent cells and down-regulates anterograde trafficking by depleting Golgi PI(4)P. Golgi localization requires oligomerization of SAC1 and recruitment of the coat protein (COP) II complex. When quiescent cells are stimulated by mitogens, SAC1 rapidly shuttles back to the endoplasmic reticulum (ER), thus releasing the brake on Golgi secretion. The p38 mitogen-activated kinase (MAPK) pathway induces dissociation of SAC1 oligomers after mitogen stimulation, which triggers COP-I–mediated retrieval of SAC1 to the ER. Inhibition of p38 MAPK abolishes growth factor–induced Golgi-to-ER shuttling of SAC1 and slows secretion. These results suggest direct roles for p38 MAPK and SAC1 in transmitting growth signals to the secretory machinery.


Current Biology | 2001

The phosphoinositide phosphatase Sac1p controls trafficking of the yeast Chs3p chitin synthase

Markus Schorr; Angela Then; Sabina Tahirovic; Nele Hug; Peter Mayinger

Phosphoinositide phosphatases play an essential but as yet not well-understood role in lipid-based signal transduction. Members of a subfamily of these enzymes share a specific domain that was first identified in the yeast Sac1 protein [1]. Sac1 homology domains were shown to exhibit 3- and 4-phosphatase activity in vitro [2, 3] and were also found, in addition to rat and yeast Sac1p, in yeast Inp/Sjl proteins [4, 5] and mammalian synaptojanins [6]. Despite the detailed in vitro characterization of the enzymatic properties of yeast Sac1p, the exact cellular function of this protein has remained obscure. We report here that Sac1p has a specific role in secretion and acts as an antagonist of the phosphatidylinositol 4-kinase Pik1p in Golgi trafficking. Elimination of Sac1p leads to excessive forward transport of chitin synthases and thus causes specific cell wall defects. Similar defects in membrane trafficking are caused by the overexpression of PIK1. Taken together, these findings provide strong evidence that the generation of PtdIns(4)P is sufficient to trigger forward transport from the Golgi to the plasma membrane and that Sac1p is critically required for the termination of this signal.


Biochimica et Biophysica Acta | 2012

Phosphoinositides and vesicular membrane traffic

Peter Mayinger

Phosphoinositide lipids were initially discovered as precursors for specific second messengers involved in signal transduction, but have now taken the center stage in controlling many essential processes at virtually every cellular membrane. In particular, phosphoinositides play a critical role in regulating membrane dynamics and vesicular transport. The unique distribution of certain phosphoinositides at specific intracellular membranes makes these molecules uniquely suited to direct organelle-specific trafficking reactions. In this regulatory role, phosphoinositides cooperate specifically with small GTPases from the Arf and Rab families. This review will summarize recent progress in the study of phosphoinositides in membrane trafficking and organellar organization and highlight the particular relevance of these signaling pathways in disease. This article is part of a Special Issue entitled Lipids and Vesicular Transport.


The EMBO Journal | 1991

A microsomal protein is involved in ATP-dependent transport of presecretory proteins into mammalian microsomes.

Peter Klappa; Peter Mayinger; Rüdiger Pipkorn; Maria Zimmermann; Richard Zimmermann

Ribonucleoparticle (i.e. ribosome and SRP)‐independent transport of proteins into mammalian microsomes is stimulated by a cytosolic ATPase which involves proteins belonging to the hsp70 family. Here we addressed the question of whether there are additional nucleoside triphosphate requirements involved in this transport mechanism. We employed a purified presecretory protein which upon solubilization in dimethyl sulfoxide and subsequent dilution into an aqueous buffer was processed by and transported into mammalian microsomes in the absence of the cytosolic ATPase. Membrane insertion of this precursor protein was found to depend on the hydrolysis of ATP and to involve a microsomal protein which can be photoaffinity inactivated with azido‐ATP. Furthermore, a microsomal protein with a similar sensitivity towards photoaffinity modification with azido‐ATP was observed to be involved in ribonucleoparticle‐dependent transport. We suggest that a novel microsomal protein which depends on ATP hydrolysis is involved in membrane insertion of both ribonucleoparticle‐dependent and ‐independent precursor proteins.


Journal of Cell Biology | 2005

Cell growth–dependent coordination of lipid signaling and glycosylation is mediated by interactions between Sac1p and Dpm1p

Frank Faulhammer; Gerlinde Konrad; Ben Brankatschk; Sabina Tahirovic; Andreas Knödler; Peter Mayinger

The integral membrane lipid phosphatase Sac1p regulates local pools of phosphatidylinositol-4-phosphate (PtdIns(4)P) at endoplasmic reticulum (ER) and Golgi membranes. PtdIns(4)P is important for Golgi trafficking, yet the significance of PtdIns(4)P for ER function is unknown. It also remains unknown how localization of Sac1p to distinct organellar membranes is mediated. Here, we show that a COOH-terminal region in yeast Sac1p is crucial for ER targeting by directly interacting with dolicholphosphate mannose synthase Dpm1p. The interaction with Dpm1p persists during exponential cell division but is rapidly abolished when cell growth slows because of nutrient limitation, causing translocation of Sac1p to Golgi membranes. Cell growth–dependent shuttling of Sac1p between the ER and the Golgi is important for reciprocal control of PtdIns(4)P levels at these organelles. The fraction of Sac1p resident at the ER is also required for efficient dolichol oligosaccharide biosynthesis. Thus, the lipid phosphatase Sac1p may be a key regulator, coordinating the secretory capacity of ER and Golgi membranes in response to growth conditions.


Traffic | 2007

Growth Control of Golgi Phosphoinositides by Reciprocal Localization of Sac1 Lipid Phosphatase and Pik1 4‐Kinase

Frank Faulhammer; Suparna Kanjilal-Kolar; Andreas Knödler; Jennifer Lo; Yerim Lee; Gerlinde Konrad; Peter Mayinger

Compartment‐specific control of phosphoinositide lipids is essential for cell function. The Sac1 lipid phosphatase regulates endoplasmic reticulum (ER) and Golgi phosphatidylinositol‐4‐phosphate [PI(4)P] in response to nutrient levels and cell growth stages. During exponential growth, Sac1p interacts with Dpm1p at the ER but shuttles to the Golgi during starvation. Here, we report that a C‐terminal region in Sac1p is required for retention in the perinuclear ER, whereas the N‐terminal domain is responsible for Golgi localization. We also show that starvation‐induced shuttling of Sac1p to the Golgi depends on the coat protein complex II and the Rer1 adaptor protein. Starvation‐induced shuttling of Sac1p to the Golgi specifically eliminates a pool of PI(4)P generated by the lipid kinase Pik1p. In addition, absence of nutrients leads to a rapid dissociation of Pik1p, together with its non‐catalytical subunit Frq1p, from Golgi membranes. Reciprocal rounds of association/dissociation of the Sac1p lipid phosphatase and the Pik1p/Frq1p lipid kinase complex are responsible for growth‐dependent control of Golgi phosphoinositides. Sac1p and Pik1p/Frq1p are therefore elements of a unique machinery that synchronizes ER and Golgi function in response to different growth conditions.


Journal of Biological Chemistry | 2002

Retention of the yeast Sac1p phosphatase in the endoplasmic reticulum causes distinct changes in cellular phosphoinositide levels and stimulates microsomal ATP transport.

Gerlinde Konrad; Tanja Schlecker; Frank Faulhammer; Peter Mayinger

The yeast phosphoinositide phosphatase Sac1p localizes to endoplasmic reticulum (ER) and Golgi membranes and has compartment-specific functions in these organelles. In this study we analyzed in detail the topology of Sac1p. Our data show that Sac1p is a type II transmembrane protein with a large N-terminal cytosolic domain, which is anchored in the membrane by the two potential transmembrane helices near the C terminus. Based on this topology, we created a mutation that caused retention of Sac1p in the ER and as a consequence showed specific alterations in cellular phosphoinositide levels. Our results suggest that Sac1p controls a pool of phosphatidylinositol 3-phosphate and phosphatidylinositol 4-phosphate in the ER. Retention of Sac1p in the ER also stimulates ATP transport into the ER lumen but causes the same Golgi-specific defects that are seen in asac1 null mutant. Taken together this study provides evidence that Sac1p is an important 4-phosphatase in the ER controlling different aspects of ER-based protein processing and secretion.


The EMBO Journal | 1999

Sac1p plays a crucial role in microsomal ATP transport, which is distinct from its function in Golgi phospholipid metabolism

Kai Ute Kochendörfer; Angela R. Then; Brian G. Kearns; Vytas A. Bankaitis; Peter Mayinger

Analysis of microsomal ATP transport in yeast resulted in the identification of Sac1p as an important factor in efficient ATP uptake into the endoplasmic reticulum (ER) lumen. Yet it remained unclear whether Sac1p is the authentic transporter in this reaction. Sac1p shows no homology to other known solute transporters but displays similarity to the N‐terminal non‐catalytic domain of a subset of inositol 5′‐phosphatases. Furthermore, Sac1p was demonstrated to be involved in inositol phospholipid metabolism, an activity whose absence contributes to the bypass Sec14p phenotype in sac1 mutants. We now show that purified recombinant Sac1p can complement ATP transport defects when reconstituted together with sac1Δ microsomal extracts, but is unable to catalyze ATP transport itself. In addition, we demonstrate that sac1Δ strains are defective in ER protein translocation and folding, which is a direct consequence of impaired ATP transport function and not related to the role of Sac1p in Golgi inositol phospholipid metabolism. These data suggest that Sac1p is an important regulator of microsomal ATP transport providing a possible link between inositol phospholipid signaling and ATP‐dependent processes in the yeast ER.


The EMBO Journal | 1993

An ATP transporter is required for protein translocation into the yeast endoplasmic reticulum.

Peter Mayinger; David I. Meyer

The transfer of precursor proteins through the membrane of the rough endoplasmic reticulum (ER) in yeast is strictly dependent on the presence of ATP. Since Kar2p (the yeast homologue of mammalian BiP) is required for translocation, and is an ATP binding protein, an ATP transport system must be coupled to the translocation machinery of the ER. We report here the characterization of a transport system for ATP in vesicles derived from yeast ER. ATP uptake into vesicles was found to be saturable in the micromolar range with a Km of 1 × 10(−5) M. ATP transport into ER vesicles was specifically inhibited by 4,4′‐diisothiocyanatostilbene‐2,2′‐disulfonic acid (DIDS), a stilbene derivative known to inhibit a number of other anion transporters, and by 3′‐O‐(4‐benzoyl)benzoyl‐ATP (Bz2‐ATP). Inhibition of ATP uptake into yeast microsomes by DIDS and Bz2‐ATP blocked protein translocation in vitro measured co‐ as well as post‐translationally. The inhibitory effect of DIDS on translocation was prevented by coincubation with ATP. Moreover, selective membrane permeabilization, allowing ATP access to the lumen, restored translocation activity to DIDS‐treated membranes. These results demonstrate that translocation requires a DIDS and Bz2‐ATP‐sensitive component whose function is to transport ATP to the lumen of the ER. These findings are consistent with current models of protein translocation in yeast which stipulate the participation of Kar2p in the translocation process.


Traffic | 2005

Regulation of intracellular phosphatidylinositol-4-phosphate by the Sac1 lipid phosphatase.

Sabina Tahirovic; Markus Schorr; Peter Mayinger

Phosphatidylinositol 4‐phosphate (PtdIns(4)P) regulates diverse cellular processes, such as actin cytoskeletal organization, Golgi trafficking and vacuolar biogenesis. Synthesis and turnover of PtdIns(4)P is mediated by a set of specific lipid kinases and phosphatases. Here we show that the polyphosphoinositide phosphatase Sac1p has a central role in compartment‐specific regulation of PtdIns(4)P. We have found that sac1Δ mutants show pleiotropic, synthetically lethal interactions with mutations in genes required for vacuolar protein sorting (Vps). Disruption of the SAC1 gene also caused a defect in the late endocytic pathway. These trafficking phenotypes correlated with a dramatic accumulation of PtdIns(4)P at vacuolar membranes. In addition, sac1 mutants displayed elevated endoplasmic reticulum PtdIns(4)P. The accumulation of PtdIns(4)P at the endoplasmic reticulum and vacuole and the endocytic defect could be compensated by mutations in the PtdIns 4‐kinase Stt4p. Our results indicate that elimination of Sac1p causes accumulation of a Stt4p‐specific PtdIns(4)P pool at internal membranes which impairs late endocytic and vacuolar trafficking. We conclude that Sac1p functions in confining PtdIns(4)P‐dependent processes to specific intracellular membranes.

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Peter Klappa

University of Göttingen

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