The role of Rab5a GTPase in endocytosis and post-endocytic trafficking of the hCG-human luteinizing hormone receptor complex

Thippeswamy Gulappa; Christine L. Clouser; K. M.J. Menon

doi:10.1007/s00018-010-0594-1

The role of Rab5a GTPase in endocytosis and post-endocytic trafficking of the hCG-human luteinizing hormone receptor complex

Thippeswamy Gulappa
, Christine L. Clouser
, K. M.J. Menon

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

Abstract

This study examined the role of Rab5a GTPase in regulating hCG-induced internalization and trafficking of the hCG-LH receptor complex in transfected 293T cells. Coexpression of wild-type Rab5a (WT) or constitutively active Rab5a (Q79L) with LHR significantly increased hCG-induced LHR internalization. Conversely, coexpression of dominant negative Rab5a (S34N) with LHR reduced internalization. Confocal microscopy showed LHR colocalizing with Rab5a (WT) and Rab5a (Q79L) in p1unctuate structures. Coexpression of Rab5a (WT) and Rab5a (Q79L) with LHR significantly increased colocalization of LHR in early endosomes. Conversely, dominant negative Rab5a (S34N) decreased this colocalization. While Rab5a stimulated internalization of LHR, it significantly decreased LHR recycling to the cell surface and increased degradation. Dominant negative Rab5a (S34N) increased LHR recycling and decreased degradation. These results suggest that Rab5a plays a role in LHR trafficking by facilitating internalization and fusion to early endosomes, increasing the degradation of internalized receptor resulting in a reduction in LHR recycling.

Original language	English (US)
Pages (from-to)	2785-2795
Number of pages	11
Journal	Cellular and Molecular Life Sciences
Volume	68
Issue number	16
DOIs	https://doi.org/10.1007/s00018-010-0594-1
State	Published - Aug 2011
Externally published	Yes

Bibliographical note

Funding Information:
This work was supported by National Institutes of Health grant R37 HD06656. We are grateful to Helle Peegel and other members of the laboratory for critical reading of the manuscript and many helpful suggestions. The confocal microscopic studies described here utilized the Morphology and Image Analysis Core (MIAC) facility at the University of Michigan Diabetes Research and training center.

Keywords

Degradation
GPCR
Internalization
LH receptor
Rab5a
Recycling
Trafficking

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10.1007/s00018-010-0594-1

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title = "The role of Rab5a GTPase in endocytosis and post-endocytic trafficking of the hCG-human luteinizing hormone receptor complex",

abstract = "This study examined the role of Rab5a GTPase in regulating hCG-induced internalization and trafficking of the hCG-LH receptor complex in transfected 293T cells. Coexpression of wild-type Rab5a (WT) or constitutively active Rab5a (Q79L) with LHR significantly increased hCG-induced LHR internalization. Conversely, coexpression of dominant negative Rab5a (S34N) with LHR reduced internalization. Confocal microscopy showed LHR colocalizing with Rab5a (WT) and Rab5a (Q79L) in p1unctuate structures. Coexpression of Rab5a (WT) and Rab5a (Q79L) with LHR significantly increased colocalization of LHR in early endosomes. Conversely, dominant negative Rab5a (S34N) decreased this colocalization. While Rab5a stimulated internalization of LHR, it significantly decreased LHR recycling to the cell surface and increased degradation. Dominant negative Rab5a (S34N) increased LHR recycling and decreased degradation. These results suggest that Rab5a plays a role in LHR trafficking by facilitating internalization and fusion to early endosomes, increasing the degradation of internalized receptor resulting in a reduction in LHR recycling.",

keywords = "Degradation, GPCR, Internalization, LH receptor, Rab5a, Recycling, Trafficking",

author = "Thippeswamy Gulappa and Clouser, \{Christine L.\} and Menon, \{K. M.J.\}",

note = "Funding Information: This work was supported by National Institutes of Health grant R37 HD06656. We are grateful to Helle Peegel and other members of the laboratory for critical reading of the manuscript and many helpful suggestions. The confocal microscopic studies described here utilized the Morphology and Image Analysis Core (MIAC) facility at the University of Michigan Diabetes Research and training center.",

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N1 - Funding Information: This work was supported by National Institutes of Health grant R37 HD06656. We are grateful to Helle Peegel and other members of the laboratory for critical reading of the manuscript and many helpful suggestions. The confocal microscopic studies described here utilized the Morphology and Image Analysis Core (MIAC) facility at the University of Michigan Diabetes Research and training center.

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AB - This study examined the role of Rab5a GTPase in regulating hCG-induced internalization and trafficking of the hCG-LH receptor complex in transfected 293T cells. Coexpression of wild-type Rab5a (WT) or constitutively active Rab5a (Q79L) with LHR significantly increased hCG-induced LHR internalization. Conversely, coexpression of dominant negative Rab5a (S34N) with LHR reduced internalization. Confocal microscopy showed LHR colocalizing with Rab5a (WT) and Rab5a (Q79L) in p1unctuate structures. Coexpression of Rab5a (WT) and Rab5a (Q79L) with LHR significantly increased colocalization of LHR in early endosomes. Conversely, dominant negative Rab5a (S34N) decreased this colocalization. While Rab5a stimulated internalization of LHR, it significantly decreased LHR recycling to the cell surface and increased degradation. Dominant negative Rab5a (S34N) increased LHR recycling and decreased degradation. These results suggest that Rab5a plays a role in LHR trafficking by facilitating internalization and fusion to early endosomes, increasing the degradation of internalized receptor resulting in a reduction in LHR recycling.

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KW - GPCR

KW - Internalization

KW - LH receptor

KW - Rab5a

KW - Recycling

KW - Trafficking

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The role of Rab5a GTPase in endocytosis and post-endocytic trafficking of the hCG-human luteinizing hormone receptor complex

Abstract

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