Related Experiment Video

Updated: Aug 10, 2026

Peptide-based Identification of Functional Motifs and their Binding Partners
14:28

Peptide-based Identification of Functional Motifs and their Binding Partners

Published on: July 1, 2013

Distinct trafficking pathways mediate Nef-induced and clathrin-dependent major histocompatibility complex class I

S Le Gall1, F Buseyne, A Trocha

  • 1Unité Rétrovirus et Transfert Génétique, URA CNRS 1930, France.

Journal of Virology
|September 12, 2000
PubMed

Insights

The human immunodeficiency virus type 1 Nef protein affects major histocompatibility complex class I (MHC-I) trafficking. Distinct pathways regulate clathrin-dependent and Nef-induced MHC-I modulation.

Area of Science:

  • Immunology
  • Virology
  • Cell Biology

Background:

  • The human immunodeficiency virus type 1 (HIV-1) Nef protein is known to modulate the surface expression of major histocompatibility complex class I (MHC-I) molecules.
  • This modulation is thought to involve alterations in the post-Golgi trafficking of MHC-I, potentially through the unmasking of a tyrosine-based sorting signal (YSQA) in the cytoplasmic tail of HLA-A and -B heavy chains.

Purpose of the Study:

  • To investigate the mechanisms by which HIV-1 Nef protein influences MHC-I trafficking.
  • To compare the effects of a prototypic sorting motif with those of Nef on MHC-I surface expression and intracellular localization.

Main Methods:

  • Genetic modification of HLA-A2 heavy chains by replacing the endogenous YSQA signal with prototypic sorting motifs (YSQI or YSQL), creating A2-endo molecules.
  • Analysis of surface expression levels and intracellular localization of modified HLA-A2 molecules in the presence or absence of Nef.
  • Utilizing a transdominant-negative mutant of dynamin-1 to assess the role of clathrin-dependent endocytosis in A2-endo trafficking and Nef activity.

Main Results:

  • Modified HLA-A2 molecules (A2-endo) exhibited constitutively low surface levels and accumulated near the Golgi apparatus, similar to wild-type HLA-A2 in Nef-expressing cells.
  • Internalization of A2-endo was rapid and associated with efficient recycling, distinct from Nef's effect on MHC-I.
  • Dynamin-1 inhibition affected A2-endo internalization and CD4 down-regulation by Nef but not Nef's effect on MHC-I, suggesting separate pathways.
  • Nef continued to affect A2-endo trafficking, indicating additive effects between prototypic signals and Nef.

Conclusions:

  • Distinct cellular trafficking pathways are involved in clathrin-dependent endocytosis and Nef-induced modulation of MHC-I.
  • The mechanisms by which prototypic sorting signals and HIV-1 Nef protein regulate MHC-I trafficking differ, despite some overlapping effects.
  • These findings contribute to understanding the complex interplay between viral proteins and host cell immune surveillance mechanisms.

More Related Videos

SorLA and CLC:CLF-1-dependent Downregulation of CNTFRα as Demonstrated by Western Blotting, Inhibition of Lysosomal Enzymes, and Immunocytochemistry10:16

SorLA and CLC:CLF-1-dependent Downregulation of CNTFRα as Demonstrated by Western Blotting, Inhibition of Lysosomal Enzymes, and Immunocytochemistry

Published on: January 6, 2017

Assessing the Expression of Major Histocompatibility Complex Class I on Primary Murine Hippocampal Neurons by Flow Cytometry08:07

Assessing the Expression of Major Histocompatibility Complex Class I on Primary Murine Hippocampal Neurons by Flow Cytometry

Published on: May 19, 2020

Related Concept Videos

Receptor-mediated Endocytosis01:38

Receptor-mediated Endocytosis

Overview
Enzyme-linked Receptors01:00

Enzyme-linked Receptors

Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
Receptor-mediated Endocytosis01:20

Receptor-mediated Endocytosis

Receptor-mediated endocytosis is when bulk amounts of specific molecules are imported into a cell after binding to cell surface receptors. The molecules bound to these receptors are taken into the cell through inward folding of the cell surface membrane, which is eventually pinched off into a vesicle within the cell. Structural proteins, such as clathrin, coat the budding vesicle.
Clathrin-Mediated Endocytosis of LDL
One well-characterized example of receptor-mediated endocytosis is the...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...
Export of Misfolded Proteins out of the ER01:32

Export of Misfolded Proteins out of the ER

After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...