Rapid cell-surface prion protein conversion revealed using a novel cell system

R Goold; S Rabbanian; L Sutton; R Andre; P Arora; J Moonga; AR Clarke; G Schiavo; P Jat; J Collinge; SJ Tabrizi

doi:10.1038/ncomms1282

Rapid cell-surface prion protein conversion revealed using a novel cell system

R Goold, S Rabbanian, L Sutton, R Andre, P Arora, J Moonga, AR Clarke, G Schiavo, P Jat, J Collinge, SJ Tabrizi

School of Biochemistry

Research output: Contribution to journal › Article (Academic Journal) › peer-review

116 Citations (Scopus)

Abstract

Prion diseases are fatal neurodegenerative disorders with unique transmissible properties. The infectious and pathological agent is thought to be a misfolded conformer of the prion protein. Little is known about the initial events in prion infection because the infecting prion source has been immunologically indistinguishable from normal cellular prion protein (PrPC). Here we develop a unique cell system in which epitope-tagged PrPC is expressed in a PrP knockdown (KD) neuroblastoma cell line. The tagged PrPC, when expressed in our PrP-KD cells, supports prion replication with the production of bona fide epitope-tagged infectious misfolded PrP (PrPSc). Using this epitope-tagged PrPSc, we study the earliest events in cellular prion infection and PrP misfolding. We show that prion infection of cells is extremely rapid occurring within 1 min of prion exposure, and we demonstrate that the plasma membrane is the primary site of prion conversion.

Translated title of the contribution	Rapid cell-surface prion protein conversion revealed using a novel cell system
Original language	English
Pages (from-to)	1 - 11
Number of pages	11
Journal	Nature Communications
Volume	2(281)
DOIs	https://doi.org/10.1038/ncomms1282
Publication status	Published - Apr 2011

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title = "Rapid cell-surface prion protein conversion revealed using a novel cell system",

abstract = "Prion diseases are fatal neurodegenerative disorders with unique transmissible properties. The infectious and pathological agent is thought to be a misfolded conformer of the prion protein. Little is known about the initial events in prion infection because the infecting prion source has been immunologically indistinguishable from normal cellular prion protein (PrPC). Here we develop a unique cell system in which epitope-tagged PrPC is expressed in a PrP knockdown (KD) neuroblastoma cell line. The tagged PrPC, when expressed in our PrP-KD cells, supports prion replication with the production of bona fide epitope-tagged infectious misfolded PrP (PrPSc). Using this epitope-tagged PrPSc, we study the earliest events in cellular prion infection and PrP misfolding. We show that prion infection of cells is extremely rapid occurring within 1 min of prion exposure, and we demonstrate that the plasma membrane is the primary site of prion conversion.",

author = "R Goold and S Rabbanian and L Sutton and R Andre and P Arora and J Moonga and AR Clarke and G Schiavo and P Jat and J Collinge and SJ Tabrizi",

year = "2011",

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doi = "10.1038/ncomms1282",

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volume = "2(281)",

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T1 - Rapid cell-surface prion protein conversion revealed using a novel cell system

AU - Goold, R

AU - Rabbanian, S

AU - Sutton, L

AU - Andre, R

AU - Arora, P

AU - Moonga, J

AU - Clarke, AR

AU - Schiavo, G

AU - Jat, P

AU - Collinge, J

AU - Tabrizi, SJ

PY - 2011/4

Y1 - 2011/4

N2 - Prion diseases are fatal neurodegenerative disorders with unique transmissible properties. The infectious and pathological agent is thought to be a misfolded conformer of the prion protein. Little is known about the initial events in prion infection because the infecting prion source has been immunologically indistinguishable from normal cellular prion protein (PrPC). Here we develop a unique cell system in which epitope-tagged PrPC is expressed in a PrP knockdown (KD) neuroblastoma cell line. The tagged PrPC, when expressed in our PrP-KD cells, supports prion replication with the production of bona fide epitope-tagged infectious misfolded PrP (PrPSc). Using this epitope-tagged PrPSc, we study the earliest events in cellular prion infection and PrP misfolding. We show that prion infection of cells is extremely rapid occurring within 1 min of prion exposure, and we demonstrate that the plasma membrane is the primary site of prion conversion.

AB - Prion diseases are fatal neurodegenerative disorders with unique transmissible properties. The infectious and pathological agent is thought to be a misfolded conformer of the prion protein. Little is known about the initial events in prion infection because the infecting prion source has been immunologically indistinguishable from normal cellular prion protein (PrPC). Here we develop a unique cell system in which epitope-tagged PrPC is expressed in a PrP knockdown (KD) neuroblastoma cell line. The tagged PrPC, when expressed in our PrP-KD cells, supports prion replication with the production of bona fide epitope-tagged infectious misfolded PrP (PrPSc). Using this epitope-tagged PrPSc, we study the earliest events in cellular prion infection and PrP misfolding. We show that prion infection of cells is extremely rapid occurring within 1 min of prion exposure, and we demonstrate that the plasma membrane is the primary site of prion conversion.

U2 - 10.1038/ncomms1282

DO - 10.1038/ncomms1282

M3 - Article (Academic Journal)

C2 - 21505437

SN - 2041-1723

VL - 2(281)

SP - 1

EP - 11

JO - Nature Communications

JF - Nature Communications

ER -

Rapid cell-surface prion protein conversion revealed using a novel cell system

Abstract

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