Role of Phosphatidylinositol(4,5)bisphosphate Organization in Membrane Transport by the Unc104 Kinesin Motor

Klopfenstein, Dieter R.; Tomishige, Michio; Stuurman, Nico; Vale, Ronald D.

doi:10.1016/s0092-8674(02)00708-0

Cited by 304 publications

(270 citation statements)

References 47 publications

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“…2C). In addition, KIF21A may recognize its cargo by interacting with acidic phospholipids in a manner that is similar to the mechanism reported for Unc104 (31). Moreover, interaction of eEF1A1 with acidic phospholipids is intriguing given its proposed function in local translation (32).…”

Section: Discussionmentioning

confidence: 63%

Proteome of Acidic Phospholipid-binding Proteins

Tsujita

Itoh

Kondo

et al. 2010

Journal of Biological Chemistry

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Reversible interactions between acidic phospholipids in the cellular membrane and proteins in the cytosol play fundamental roles in a wide variety of physiological events. Here, we present a novel approach to the identification of acidic phospholipid-binding proteins using nano-liquid chromatography-tandem mass spectrometry. We found more than 400 proteins, including proteins with previously known acidic phospholipid-binding properties, and confirmed that several candidates, such as Coronin 1A, mDia1 (Diaphanous-related formin-1), PIR121/CYFIP2, EB2 (end plus binding protein-2), KIF21A (kinesin family member 21A), eEF1A1 (translation elongation factor 1␣1), and TRIM2, directly bind to acidic phospholipids. Among such novel proteins, we provide evidence that Coronin 1A activity, which disassembles Arp2/3-containing actin filament branches, is spatially and temporally regulated by phosphatidylinositol 4,5-bisphosphate (PI(4,5)P 2 ). Whereas Coronin 1A co-localizes with PI(4,5)P 2 at the plasma membrane in resting cells, it is dissociated from the plasma membrane during lamellipodia formation where the PI(4,5)P 2 signal is significantly reduced. Our in vitro experiments show that Coronin 1A preferentially binds to PI(4,5)P 2 -containing liposomes and that PI(4,5)P 2 antagonizes the ability of Coronin 1A to disassemble actin filament branches, indicating a spatiotemporal regulation of Coronin 1A via a direct interaction with the plasma membrane lipid. Collectively, our proteomics data provide a list of potential acidic phospholipid-binding protein candidates ranging from the actin regulatory proteins to translational regulators.

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Section: Discussionmentioning

confidence: 63%

Proteome of Acidic Phospholipid-binding Proteins

Tsujita

Itoh

Kondo

et al. 2010

Journal of Biological Chemistry

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“…Thus PtdIns(4)P functions in maintaining Golgi structure both directly and through conversion to PtdIns(4,5)P 2 , probably by recruiting cytoskeleton to Golgi membranes and by maintaining the flux of membrane moving through the organelle. One explanation for why PtdIns(4,5)P 2 levels might be relatively low on Golgi membranes is that the 5-phosphatase OCRL on that organelle (87) might rapidly convert Golgi PtdIns(4,5)P 2 back to PtdIns(4)P. Another possibility is the remarkable observation that a kinesin, unc104/KIF1A, binds preferentially to vesicles containing PtdIns(4,5)P 2 (185). The ability of unc104/KIF1A to move vesicles is sharply dependent on the concentration of PtdIns(4,5)P 2 , and if that lipid is generated at the site of vesicle budding to recruit and activate a motor, PtdIns(4,5)P 2 might be rapidly exported with the vesicle, keeping the pool of free PtdIns(4,5)P 2 on the Golgi low.…”

Section: E Ptdins(4)p and Ptdins(45)p 2 On The Golgimentioning

confidence: 99%

“…The ability of unc104/KIF1A to move vesicles is sharply dependent on the concentration of PtdIns(4,5)P 2 , and if that lipid is generated at the site of vesicle budding to recruit and activate a motor, PtdIns(4,5)P 2 might be rapidly exported with the vesicle, keeping the pool of free PtdIns(4,5)P 2 on the Golgi low. The concentration of PtdIns(4,5)P 2 required to activate the motor is lowered when raft-forming lipids are added to the vesicles (185). This suggests that raft lipids, cholesterol and glycospingolipids, may serve to concentrate PtdIns(4,5)P 2 and enhance binding of the vesicle to the motor.…”

Section: E Ptdins(4)p and Ptdins(45)p 2 On The Golgimentioning

confidence: 99%

Phosphoinositides in Constitutive Membrane Traffic

Roth

2004

Physiological Reviews

263

267

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Proteins that make, consume, and bind to phosphoinositides are important for constitutive membrane traffic. Different phosphoinositides are concentrated in different parts of the central vacuolar pathway, with phosphatidylinositol 4-phosphate predominate on Golgi, phosphatidylinositol 4,5-bisphosphate predominate at the plasma membrane, phosphatidylinositol 3-phosphate the major phosphoinositide on early endosomes, and phosphatidylinositol 3,5-bisphosphate found on late endocytic organelles. This spatial segregation may be the mechanism by which the direction of membrane traffic is controlled. Phosphoinositides increase the affinity of membranes for peripheral membrane proteins that function for sorting protein cargo or for the docking and fusion of transport vesicles. This implies that constitutive membrane traffic may be regulated by the mechanisms that control the activity of the enzymes that produce and consume phosphoinositides. Although the lipid kinases and phosphatases that function in constitutive membrane traffic are beginning to be identified, their regulation is poorly understood.

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“…Injection of beads coated with only one type of protein into the axon allowed us to test directly whether any protein on its own was sufficient for transport independent of other organelle motor receptors. These studies do not address whether APP is necessary for cargo transport, which is unlikely because there may be many ways for cargo to recruit motors, including binding to lipids (19).…”

Section: Transport Of App Beads Resembles Physiological Fast Axonal Tmentioning

confidence: 99%

A peptide zipcode sufficient for anterograde transport within amyloid precursor protein

Satpute-Krishnan

DeGiorgis

Conley

et al. 2006

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

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Fast anterograde transport of membrane-bound organelles delivers molecules synthesized in the neuronal cell body outward to distant synapses. Identification of the molecular ''zipcodes'' on organelles that mediate attachment and activation of microtubulebased motors for this directed transport is a major area of inquiry. Here we identify a short peptide sequence (15 aa) from the cytoplasmic C terminus of amyloid precursor protein (APP-C) sufficient to mediate the anterograde transport of peptide-conjugated beads in the squid giant axon. APP-C beads travel at fast axonal transport rates (0.53 m͞s average velocity, 0.9 m͞s maximal velocity) whereas beads coupled to other peptides coinjected into the same axon remain stationary at the injection site. This transport appears physiologic, because it mimics behavior of endogenous squid organelles and of beads conjugated to C99, a polypeptide containing the full-length cytoplasmic domain of amyloid precursor protein (APP). Beads conjugated to APP lacking the APP-C domain are not transported. Coinjection of APP-C peptide reduces C99 bead motility by 75% and abolishes APP-C bead motility, suggesting that the soluble peptide competes with protein-conjugated beads for axoplasmic motor(s). The APP-C domain is conserved (13͞15 aa) from squid to human, and peptides from either squid or human APP behave similarly. Thus, we have identified a conserved peptide zipcode sufficient to direct anterograde transport of exogenous cargo and suggest that one of APP's roles may be to recruit and activate axonal machinery for endogenous cargo transport.fast axonal transport ͉ herpes simplex virus ͉ kinesin anterograde transport ͉ squid giant axon

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Role of Phosphatidylinositol(4,5)bisphosphate Organization in Membrane Transport by the Unc104 Kinesin Motor

Cited by 304 publications

References 47 publications

Proteome of Acidic Phospholipid-binding Proteins

Proteome of Acidic Phospholipid-binding Proteins

Phosphoinositides in Constitutive Membrane Traffic

A peptide zipcode sufficient for anterograde transport within amyloid precursor protein

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