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Analyses of the recycling receptor, FcRn, in live cells reveal novel pathways for lysosomal delivery

Analyses of the recycling receptor, FcRn, in live cells reveal novel pathways for lysosomal delivery
Analyses of the recycling receptor, FcRn, in live cells reveal novel pathways for lysosomal delivery

Lysosomes play a central role in the degradation of proteins and other macromolecules. The mechanisms by which receptors are transferred to lysosomes for constitutive degradation are poorly understood. We have analyzed the processes that lead to the lysosomal delivery of the Fc receptor, FcRn. These studies provide support for a novel pathway for receptor delivery. Specifically, unlike other receptors that enter intraluminal vesicles in late endosomes, FcRn is transferred from the limiting membrane of such endosomes to lysosomes, and is rapidly internalized into the lysosomal lumen. By contrast, LAMP-1 persists on the limiting membrane. Receptor transfer is mediated by tubular extensions from late endosomes to lysosomes, or by interactions of the two participating organelles in kiss-and-linger-like processes, whereas full fusion is rarely observed. The persistence of FcRn on the late endosomal limiting membrane, together with selective transfer to lysosomes, allows this receptor to undergo recycling or degradation. Consequently, late endosomes have functional plasticity, consistent with the presence of the Rab5 GTPase in discrete domains on these compartments. Copyright Journal compilation

Endosomal trafficking, FcRn, LAMP-1, Lysosome, Rab GTPase
1398-9219
600-614
Gan, Zhuo
cc085ff5-6cca-4337-a4ae-7be99c5e6032
Ram, Sripad
559bd560-3817-4e53-8c7a-2f08e4518412
Vaccaro, Carlos
f576072e-379e-4f42-9bd7-595b2f5b7d58
Ober, Raimund J.
31f4d47f-fb49-44f5-8ff6-87fc4aff3d36
Ward, Sally E.
b31c0877-8abe-485f-b800-244a9d3cd6cc
Gan, Zhuo
cc085ff5-6cca-4337-a4ae-7be99c5e6032
Ram, Sripad
559bd560-3817-4e53-8c7a-2f08e4518412
Vaccaro, Carlos
f576072e-379e-4f42-9bd7-595b2f5b7d58
Ober, Raimund J.
31f4d47f-fb49-44f5-8ff6-87fc4aff3d36
Ward, Sally E.
b31c0877-8abe-485f-b800-244a9d3cd6cc

Gan, Zhuo, Ram, Sripad, Vaccaro, Carlos, Ober, Raimund J. and Ward, Sally E. (2009) Analyses of the recycling receptor, FcRn, in live cells reveal novel pathways for lysosomal delivery. Traffic, 10 (5), 600-614. (doi:10.1111/j.1600-0854.2009.00887.x).

Record type: Article

Abstract

Lysosomes play a central role in the degradation of proteins and other macromolecules. The mechanisms by which receptors are transferred to lysosomes for constitutive degradation are poorly understood. We have analyzed the processes that lead to the lysosomal delivery of the Fc receptor, FcRn. These studies provide support for a novel pathway for receptor delivery. Specifically, unlike other receptors that enter intraluminal vesicles in late endosomes, FcRn is transferred from the limiting membrane of such endosomes to lysosomes, and is rapidly internalized into the lysosomal lumen. By contrast, LAMP-1 persists on the limiting membrane. Receptor transfer is mediated by tubular extensions from late endosomes to lysosomes, or by interactions of the two participating organelles in kiss-and-linger-like processes, whereas full fusion is rarely observed. The persistence of FcRn on the late endosomal limiting membrane, together with selective transfer to lysosomes, allows this receptor to undergo recycling or degradation. Consequently, late endosomes have functional plasticity, consistent with the presence of the Rab5 GTPase in discrete domains on these compartments. Copyright Journal compilation

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More information

e-pub ahead of print date: 24 January 2009
Published date: 8 April 2009
Keywords: Endosomal trafficking, FcRn, LAMP-1, Lysosome, Rab GTPase

Identifiers

Local EPrints ID: 423601
URI: http://eprints.soton.ac.uk/id/eprint/423601
ISSN: 1398-9219
PURE UUID: 52dde8d2-5b13-42db-bc2b-a488db9ec8ef
ORCID for Raimund J. Ober: ORCID iD orcid.org/0000-0002-1290-7430
ORCID for Sally E. Ward: ORCID iD orcid.org/0000-0003-3232-7238

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Date deposited: 27 Sep 2018 16:30
Last modified: 16 Mar 2024 04:37

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Contributors

Author: Zhuo Gan
Author: Sripad Ram
Author: Carlos Vaccaro
Author: Raimund J. Ober ORCID iD
Author: Sally E. Ward ORCID iD

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