Limits...
Dangerous liaisons between a microbe and the prion protein.

Aguzzi A, Hardt WD - J. Exp. Med. (2003)

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, University Hospital of Zürich, Schmelzbergstr. 12, CH-8091 Zürich, Switzerland. adriano@pathol.unizh.ch

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

For playing these tricks, Brucella relies on a set of virulence factors, including a bacterial injection organelle termed VirB or type IV secretion system... There, Hsp60 appears to snatch at an unlikely friend, the cellular prion protein (PrP), which is encoded by the Prnp gene and resides preferentially in rafts... PrP is apparently recruited to the macrophage's membrane protrusions, which engulf the bacteria, and subsequently to the early macropinosome... In Prnp macrophages, B. abortus does not modulate phagocytosis nor phagosome maturation... The latter presumption is backed up by animal studies... Wild-type Brucella replicates in wild-type mice, whereas virB mutants do not... This phenotype is only observed in Prnp mice and is fully reverted by substoichiometric coexpression of full-length PrP... It follows that truncated PrP interferes with a physiological function of PrP and that its effector domain lies in its amino proximal half... Selective pressure to maintain heterozygosity might have come from Kuru, a cannibalism-transmitted prion disease that was a prime cause of death in New Guinea tribes... One disturbing conclusion is that cannibalism was commonplace among our ancestors... Hence, the function of the type IV secretion system must go beyond surface exposure of Hsp60... Which effector proteins travel via this pathway and what is their function? Does Brucella interfere with the function of PrP? Interestingly, some of these bugs (mycobacteria, C. trachomatis, and certain E. coli strains ) need, like Brucella, intact lipid rafts on the host cell surface to reach this niche.

Show MeSH
Macrophage manipulation by B. abortus: A role for the Hsp60–PrPC interaction. B. abortus transports Hsp60 via the VirB type IV system onto its surface. Upon encounter with a macrophage, Hsp60 binds to PrPC, which is embedded in lipid rafts on the macrophage surface. This is thought to modulate phagocytosis (swimming internalization), mediate macropinosome formation, inhibit lysosome fusion, and steer the macropinosome to the formation of the replicative phagosome. Other, hitherto unknown effector proteins traveling via the VirB system are also involved (see text; based on the findings by Watarai et al. [reference 1]).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2196075&req=5

fig1: Macrophage manipulation by B. abortus: A role for the Hsp60–PrPC interaction. B. abortus transports Hsp60 via the VirB type IV system onto its surface. Upon encounter with a macrophage, Hsp60 binds to PrPC, which is embedded in lipid rafts on the macrophage surface. This is thought to modulate phagocytosis (swimming internalization), mediate macropinosome formation, inhibit lysosome fusion, and steer the macropinosome to the formation of the replicative phagosome. Other, hitherto unknown effector proteins traveling via the VirB system are also involved (see text; based on the findings by Watarai et al. [reference 1]).

Mentions: Brucella actively modulates its own engulfment. It induces peculiar membrane ruffles at its site of contact with the macrophage and slow “swimming internalization” into a macropinosome. Then, Brucella takes full control of the macropinosome. It inhibits its maturation into a degradative lysosome (3) and reprograms it to acquire endoplasmic reticulum markers and mature into a “replicative phagosome” where bacteria start multiplying (Fig. 1; reference 2).


Dangerous liaisons between a microbe and the prion protein.

Aguzzi A, Hardt WD - J. Exp. Med. (2003)

Macrophage manipulation by B. abortus: A role for the Hsp60–PrPC interaction. B. abortus transports Hsp60 via the VirB type IV system onto its surface. Upon encounter with a macrophage, Hsp60 binds to PrPC, which is embedded in lipid rafts on the macrophage surface. This is thought to modulate phagocytosis (swimming internalization), mediate macropinosome formation, inhibit lysosome fusion, and steer the macropinosome to the formation of the replicative phagosome. Other, hitherto unknown effector proteins traveling via the VirB system are also involved (see text; based on the findings by Watarai et al. [reference 1]).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2196075&req=5

fig1: Macrophage manipulation by B. abortus: A role for the Hsp60–PrPC interaction. B. abortus transports Hsp60 via the VirB type IV system onto its surface. Upon encounter with a macrophage, Hsp60 binds to PrPC, which is embedded in lipid rafts on the macrophage surface. This is thought to modulate phagocytosis (swimming internalization), mediate macropinosome formation, inhibit lysosome fusion, and steer the macropinosome to the formation of the replicative phagosome. Other, hitherto unknown effector proteins traveling via the VirB system are also involved (see text; based on the findings by Watarai et al. [reference 1]).
Mentions: Brucella actively modulates its own engulfment. It induces peculiar membrane ruffles at its site of contact with the macrophage and slow “swimming internalization” into a macropinosome. Then, Brucella takes full control of the macropinosome. It inhibits its maturation into a degradative lysosome (3) and reprograms it to acquire endoplasmic reticulum markers and mature into a “replicative phagosome” where bacteria start multiplying (Fig. 1; reference 2).

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, University Hospital of Zürich, Schmelzbergstr. 12, CH-8091 Zürich, Switzerland. adriano@pathol.unizh.ch

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

For playing these tricks, Brucella relies on a set of virulence factors, including a bacterial injection organelle termed VirB or type IV secretion system... There, Hsp60 appears to snatch at an unlikely friend, the cellular prion protein (PrP), which is encoded by the Prnp gene and resides preferentially in rafts... PrP is apparently recruited to the macrophage's membrane protrusions, which engulf the bacteria, and subsequently to the early macropinosome... In Prnp macrophages, B. abortus does not modulate phagocytosis nor phagosome maturation... The latter presumption is backed up by animal studies... Wild-type Brucella replicates in wild-type mice, whereas virB mutants do not... This phenotype is only observed in Prnp mice and is fully reverted by substoichiometric coexpression of full-length PrP... It follows that truncated PrP interferes with a physiological function of PrP and that its effector domain lies in its amino proximal half... Selective pressure to maintain heterozygosity might have come from Kuru, a cannibalism-transmitted prion disease that was a prime cause of death in New Guinea tribes... One disturbing conclusion is that cannibalism was commonplace among our ancestors... Hence, the function of the type IV secretion system must go beyond surface exposure of Hsp60... Which effector proteins travel via this pathway and what is their function? Does Brucella interfere with the function of PrP? Interestingly, some of these bugs (mycobacteria, C. trachomatis, and certain E. coli strains ) need, like Brucella, intact lipid rafts on the host cell surface to reach this niche.

Show MeSH