Muskelin Coordinates PrP Lysosome versus Exosome Targeting and Impacts Prion Disease Progression

Frank F Heisler; Yvonne Pechmann; Ines Wieser; Hermann C Altmeppen; Leonhard Veenendaal; Mary Muhia; Michaela Schweizer; Markus Glatzel; Susanne Krasemann; Matthias Kneussel

doi:10.1016/j.neuron.2018.08.010

Muskelin Coordinates PrP Lysosome versus Exosome Targeting and Impacts Prion Disease Progression

Standard

Muskelin Coordinates PrP Lysosome versus Exosome Targeting and Impacts Prion Disease Progression. / Heisler, Frank F; Pechmann, Yvonne; Wieser, Ines; Altmeppen, Hermann C; Veenendaal, Leonhard; Muhia, Mary; Schweizer, Michaela ; Glatzel, Markus ; Krasemann, Susanne ; Kneussel, Matthias.

In: NEURON, Vol. 99, No. 6, 19.09.2018, p. 1155-1169.e9.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Heisler, FF, Pechmann, Y, Wieser, I, Altmeppen, HC, Veenendaal, L, Muhia, M, Schweizer, M , Glatzel, M , Krasemann, S & Kneussel, M 2018, 'Muskelin Coordinates PrP Lysosome versus Exosome Targeting and Impacts Prion Disease Progression', NEURON, vol. 99, no. 6, pp. 1155-1169.e9. https://doi.org/10.1016/j.neuron.2018.08.010

APA

Heisler, F. F., Pechmann, Y., Wieser, I., Altmeppen, H. C., Veenendaal, L., Muhia, M., Schweizer, M., Glatzel, M., Krasemann, S., & Kneussel, M. (2018). Muskelin Coordinates PrP Lysosome versus Exosome Targeting and Impacts Prion Disease Progression. NEURON, 99(6), 1155-1169.e9. https://doi.org/10.1016/j.neuron.2018.08.010

Vancouver

Heisler FF, Pechmann Y, Wieser I, Altmeppen HC, Veenendaal L, Muhia M et al. Muskelin Coordinates PrP Lysosome versus Exosome Targeting and Impacts Prion Disease Progression. NEURON. 2018 Sep 19;99(6):1155-1169.e9. https://doi.org/10.1016/j.neuron.2018.08.010

Bibtex

@article{e6d148ffebd44d79afe780c58ce5136a,

title = "Muskelin Coordinates PrP Lysosome versus Exosome Targeting and Impacts Prion Disease Progression",

abstract = "Cellular prion protein (PrPC) modulates cell adhesion and signaling in the brain. Conversion to its infectious isoform causes neurodegeneration, including Creutzfeldt-Jakob disease in humans. PrPC undergoes rapid plasma membrane turnover and extracellular release via exosomes. However, the intracellular transport of PrPC and its potential impact on prion disease progression is barely understood. Here we identify critical components of PrPC trafficking that also link intracellular and extracellular PrPC turnover. PrPC associates with muskelin, dynein, and KIF5C at transport vesicles. Notably, muskelin coordinates bidirectional PrPC transport and facilitates lysosomal degradation over exosomal PrPC release. Muskelin gene knockout consequently causes PrPC accumulation at the neuronal surface and on secreted exosomes. Moreover, prion disease onset is accelerated following injection of pathogenic prions into muskelin knockout mice. Our data identify an essential checkpoint in PrPC turnover. They propose a novel connection between neuronal intracellular lysosome targeting and extracellular exosome trafficking, relevant to the pathogenesis of neurodegenerative conditions.",

keywords = "Journal Article",

author = "Heisler, {Frank F} and Yvonne Pechmann and Ines Wieser and Altmeppen, {Hermann C} and Leonhard Veenendaal and Mary Muhia and Michaela Schweizer and Markus Glatzel and Susanne Krasemann and Matthias Kneussel",

year = "2018",

month = sep,

day = "19",

doi = "10.1016/j.neuron.2018.08.010",

language = "English",

volume = "99",

pages = "1155--1169.e9",

journal = "NEURON",

issn = "0896-6273",

publisher = "Cell Press",

number = "6",

}

RIS

TY - JOUR

T1 - Muskelin Coordinates PrP Lysosome versus Exosome Targeting and Impacts Prion Disease Progression

AU - Heisler, Frank F

AU - Pechmann, Yvonne

AU - Wieser, Ines

AU - Altmeppen, Hermann C

AU - Veenendaal, Leonhard

AU - Muhia, Mary

AU - Schweizer, Michaela

AU - Glatzel, Markus

AU - Krasemann, Susanne

AU - Kneussel, Matthias

PY - 2018/9/19

Y1 - 2018/9/19

N2 - Cellular prion protein (PrPC) modulates cell adhesion and signaling in the brain. Conversion to its infectious isoform causes neurodegeneration, including Creutzfeldt-Jakob disease in humans. PrPC undergoes rapid plasma membrane turnover and extracellular release via exosomes. However, the intracellular transport of PrPC and its potential impact on prion disease progression is barely understood. Here we identify critical components of PrPC trafficking that also link intracellular and extracellular PrPC turnover. PrPC associates with muskelin, dynein, and KIF5C at transport vesicles. Notably, muskelin coordinates bidirectional PrPC transport and facilitates lysosomal degradation over exosomal PrPC release. Muskelin gene knockout consequently causes PrPC accumulation at the neuronal surface and on secreted exosomes. Moreover, prion disease onset is accelerated following injection of pathogenic prions into muskelin knockout mice. Our data identify an essential checkpoint in PrPC turnover. They propose a novel connection between neuronal intracellular lysosome targeting and extracellular exosome trafficking, relevant to the pathogenesis of neurodegenerative conditions.

AB - Cellular prion protein (PrPC) modulates cell adhesion and signaling in the brain. Conversion to its infectious isoform causes neurodegeneration, including Creutzfeldt-Jakob disease in humans. PrPC undergoes rapid plasma membrane turnover and extracellular release via exosomes. However, the intracellular transport of PrPC and its potential impact on prion disease progression is barely understood. Here we identify critical components of PrPC trafficking that also link intracellular and extracellular PrPC turnover. PrPC associates with muskelin, dynein, and KIF5C at transport vesicles. Notably, muskelin coordinates bidirectional PrPC transport and facilitates lysosomal degradation over exosomal PrPC release. Muskelin gene knockout consequently causes PrPC accumulation at the neuronal surface and on secreted exosomes. Moreover, prion disease onset is accelerated following injection of pathogenic prions into muskelin knockout mice. Our data identify an essential checkpoint in PrPC turnover. They propose a novel connection between neuronal intracellular lysosome targeting and extracellular exosome trafficking, relevant to the pathogenesis of neurodegenerative conditions.

KW - Journal Article

U2 - 10.1016/j.neuron.2018.08.010

DO - 10.1016/j.neuron.2018.08.010

M3 - SCORING: Journal article

C2 - 30174115

VL - 99

SP - 1155-1169.e9

JO - NEURON

JF - NEURON

SN - 0896-6273

IS - 6

ER -