Modulation of Receptor Recycling and Degradation by the Endosomal Kinesin KIF16B

Hoepfner, Sebastian; Severin, Fedor F.; Cabezas, Alicia; Habermann, Bianca; Runge, Anja; Gillooly, David J.; Stenmark, Harald; Zerial, Marino

doi:10.1016/j.cell.2005.02.017

Cited by 292 publications

(313 citation statements)

References 51 publications

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“…The plus-end directed motor protein Kif16b, also known as SNX23, is targeted via its PI(3)P-binding PX-domain to early endosomes, dependent on Rab5 and Vps34 activity. Thus, Kif16b is required for endosome positioning and efficient early endosomal recycling (Hoepfner, Severin et al 2005). …”

Section: Figure 3: Tubular Cargo-enriched Subdomains At the Early Sormentioning

confidence: 99%

“…Loss of Kif16b, a plus-end directed, PI(3)P-dependent kinesin (Hoepfner, Severin et al 2005), abolished outward transport and resulted in a more concentrated perinuclear localization of TfR without affecting exocytosis. Consistent with (2), depletion of Kif16b together with MTM1 restored perinuclear TfR localization, while it could not rescue the exocytic defect (Figure 27).…”

Section: Pi(3)p Levels Can Be Manipulated By Genetic and Pharmacologimentioning

confidence: 99%

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A phosphoinositide conversion mechanism for exit from endosomes

Ketel¹,

Krauß²,

Nicot³

et al. 2016

Nature

157

177

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I owe special thanks to Marnix Wieffer and Michael Krauß, who spent a lot of time helping me to get started in the lab, to overcome numerous experimental problem, I was not sure how to deal with, and frequently joined in discussions about my project with excellent advice. I am really grateful for your experimental support, Michael, and the time you invested in the project during our paper revision.Further, I would like to thank Jocelyn Laporte and his group, especially Anne-Sophie Nicot, at the IGBMC in Strasbourg for their support and a very fruitful collaboration, and Carsten Schultz and his group at the EMBL in Heidelberg for their support and constant supply with PIP/AMs. I owe special thanks to Dmytro Puchkov for the ultrastructural analysis and Eberhard Krause for mass spectrometry done within this project. I also need to acknowledge Markus Wenk and Federico Torta at the Singapore Lipidomics Incubator for joining the project at a very late stage, when we urgently needed help from lipidomics specialists. It was a pity that experiments did not work out as planned.I would further like to express my gratitude to two very skilled technicians in the AG Haucke lab: Silke Zillmann and Delia Löwe. Without your help it would have been impossible to achieve so much within the limited amount of time I had during the paper revision. by VPS34-IN1 treatment................................................... 52 2.3.11 Fluorescence microscopy................................................................................. 53 2.3.12 Flow cytometry............................................................................................ III SummaryPhosphoinositides (PIs) are a minor class of short-lived phospholipids that serve as crucial signposts of membrane identity. Thereby, PIs full fill important functions in cell signaling and membrane transport. PI 4-phosphates such as phosphatitylinositol-4-phosphate (PI(4)P) and phosphatitylinositol-4,5-bisphosphate (PI(4,5)P 2 ) are enriched at the plasma membrane (PM), on secretory organelles and lysosomes, while PI 3-phosphates, i.e.phosphatitylinositol-3-phosphate (PI(3)P), are a hallmark of the endosomal system.Directional transport between these compartments, thus, requires regulated PI conversion.However, PI conversion in exit from PI(3)P-enriched endosomes en route to the PI(4)P-and PI(4,5)P 2 -positive PM in endosomal recycling remained unknown.Here, we report that cargo exit from endosomes requires removal of PI(3)P by the PI(3)P 3-phosphatase myotubularin 1 (MTM1), and concomitant PI(4)P synthesis by PI 4-kinase type II α (PI4K2α). Loss of MTM1 causes endosomal accumulation of PI(3)P and PI(3)P effector proteins, i.e. sorting nexins, Kif16b-mediated outward traffic of PI(3)P containing endosomes and sub-plasmalemmal accumulation of exocytosis-deficient endosomes. As PI4K2α associates with MTM1 and thereby facilitates membrane recruitment of MTM1, these phenotypic changes are mimicked by loss of PI4K2α. The conversion of PI(3)P-to-PI(4)P is paralleled by a switch i...

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Section: Figure 3: Tubular Cargo-enriched Subdomains At the Early Sormentioning

confidence: 99%

Section: Pi(3)p Levels Can Be Manipulated By Genetic and Pharmacologimentioning

confidence: 99%

A phosphoinositide conversion mechanism for exit from endosomes

Ketel¹,

Krauß²,

Nicot³

et al. 2016

Nature

157

177

View full text Add to dashboard Cite

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“…Zerial and coworkers (Hoepfner et al, 2005) have recently shown that PI3P generation is not only accompanied by the recruitment of EEA1 but also regulates the loading of the pleckstrin homology domain bearing Kinesin family protein KIF16B. KIF16B is a plus-end-directed motor and mediates transport of early endosomes along microtubules; therefore, it regulates the steady-state distribution of early endosomes (Hoepfner et al, 2005).…”

Section: Pi3k and Cellular Localization Of Geecsmentioning

confidence: 99%

“…These results suggest a mechanism where the level of EEA1 recruitment is important for correct targeting during heterotypic fusion. Inhibition of PI3K activity also inhibits fusion between GEECs, suggesting that similar machinery may function in effecting fusion between GEECs.Zerial and coworkers (Hoepfner et al, 2005) have recently shown that PI3P generation is not only accompanied by the recruitment of EEA1 but also regulates the loading of the pleckstrin homology domain bearing Kinesin family protein KIF16B. KIF16B is a plus-end-directed motor and mediates transport of early endosomes along microtubules; therefore, it regulates the steady-state distribution of early endosomes (Hoepfner et al, 2005).…”

mentioning

confidence: 99%

Arf6-independent GPI-anchored Protein-enriched Early Endosomal Compartments Fuse with Sorting Endosomes via a Rab5/Phosphatidylinositol-3′-Kinase–dependent Machinery

Kalia

Kumari

Chadda

et al. 2006

MBoC

105

117

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In the process of internalization of molecules from the extracellular milieu, a cell uses multiple endocytic pathways, consequently generating different endocytic vesicles. These primary endocytic vesicles are targeted to specific destinations inside the cell. Here, we show that GPI-anchored proteins are internalized by an Arf6-independent mechanism into GPI-anchored protein-enriched early endosomal compartments (GEECs). Internalized GPI-anchored proteins and the fluid phase are first visualized in GEECs that are acidic, primary endocytic structures, negative for early endosomal markers, Rab4, Rab5, and early endosome antigen (EEA)1. They subsequently acquire Rab5 and EEA1 before homotypic fusion with other GEECs, and heterotypic fusion with endosomes containing cargo from the clathrin-dependent endocytic pathway. Although, the formation of GEECs is unaffected by inhibition of Rab5 GTPase and phosphatidylinositol-3 -kinase (PI3K) activity, their fusion with sorting endosomes is dependent on both activities. Overexpression of Rab5 reverts PI3K inhibition of fusion, providing evidence that Rab5 effectors play important roles in heterotypic fusion between the dynamin-independent GEECs and clathrin-and dynamin-dependent sorting endosomes. INTRODUCTIONA cell uses multiple endocytic pathways for the uptake of molecules from the extracellular milieu (Mukherjee et al., 1997;Conner and Schmid, 2003). The better characterized pathways are mediated by clathrin-and caveolae-coated endocytic invaginations and require dynamin activity to be severed from the plasma membrane (Damke et al., 1994;Hinshaw and Schmid, 1995;Henley et al., 1998;Oh et al., 1998). There also seem to be one or more clathrin-independent pathways where dynamin is required, for example, the pathway for internalization of the interleukin (IL)-2 receptor subunits (Lamaze et al., 2001). In addition, there are a growing number of dynamin-independent endocytic processes that serve as internalization routes for a number of cell surface proteins, including lipid-linked proteins, such as GPI-anchored proteins (Lamaze and Schmid, 1995;Conner and Schmid, 2003;Nichols, 2003;Mayor and Riezman, 2004;Naslavsky et al., 2004;.GPI-anchored proteins are internalized via a dynamin, caveolin, and clathrin-independent pathway that is also responsible for the entry of a sizable fraction of the fluid phase in a number of cell types (Fivaz et al., 2002;Sabharanjak et al., 2002;Guha et al., 2003;. GPI-anchored proteins and the fluid phase enter the cell via tubular invaginations at the cell surface, into compartments termed GPI-anchored protein-enriched early endosomal compartments (GEECs) . At early times, these structures are largely devoid of cargo from the clathrin-dependent pathway. Besides a requirement for the small GTPase cdc42, very little is known about the molecular players that govern the formation and trafficking of GEECs. Much less is known about the detailed endocytic itinerary of these pathways (Lamaze and Schmid, 1995;Mayor and Riezman, 2004).After internalization...

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“…Microtubules are polarised, with the plus-end usually pointing towards the cell membrane, away from the nucleus [40]. There are numerous articles providing supporting evidence as to which motor proteins are involved in each stage of the process, although they do not always agree [3,5,12,23,33]. These differences may be due to the differences in results from the studies of different types of cells, experimental techniques and differences between in vitro and in vivo studies.…”

Section: Introductionmentioning

confidence: 99%

From the Cell Membrane to the Nucleus: Unearthing Transport Mechanisms for Dynein

et al. 2012

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Mutations in the motor protein cytoplasmic dynein have been found to cause Charcot-MarieTooth disease in humans, spinal muscular atrophy and severe intellectual disabilities in humans.In mouse models neurodegeneration is observed. We sought to develop a novel model which could incorporate the effect of mutations on distance travelled and velocity. A mechanical model for the dynein mediated transport of endosomes is derived from first principles and solved numerically. The effects of variations in model parameter values are analysed to find those that have a significant impact on velocity and distance travelled. The model successfully describes the processivity of dynein and matches qualitatively the velocity profiles observed in experiments.

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Modulation of Receptor Recycling and Degradation by the Endosomal Kinesin KIF16B

Cited by 292 publications

References 51 publications

A phosphoinositide conversion mechanism for exit from endosomes

A phosphoinositide conversion mechanism for exit from endosomes

Arf6-independent GPI-anchored Protein-enriched Early Endosomal Compartments Fuse with Sorting Endosomes via a Rab5/Phosphatidylinositol-3′-Kinase–dependent Machinery

From the Cell Membrane to the Nucleus: Unearthing Transport Mechanisms for Dynein

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