Lack of Tyrosine 320 Impairs Spontaneous Endocytosis and Enhances Release of HLA-B27 Molecules

Santos, Susana G.; Antoniou, Antony N.; Sampaio, Paula; Powis, Simon J.; Arosa, Fernando A.

doi:10.4049/jimmunol.176.5.2942

Cited by 26 publications

(33 citation statements)

References 38 publications

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“…The endocytosis of MHC class I molecules is dependent on a sequence in the MHC class I molecule cytoplasmic tail (40,41,47). Studies have indicated that MHC class I molecules are recycled to the cell surface after internalization (e.g.…”

Section: Discussionmentioning

confidence: 99%

Mechanism for Amyloid Precursor-like Protein 2 Enhancement of Major Histocompatibility Complex Class I Molecule Degradation

Tuli

Sharma

Capek

et al. 2009

Journal of Biological Chemistry

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Earlier studies have demonstrated interaction of the murine major histocompatibility complex (MHC) class I molecule K d with amyloid precursor-like protein 2 (APLP2), a ubiquitously expressed member of the amyloid precursor protein family. Our current findings indicate that APLP2 is internalized in a clathrindependent manner, as shown by utilization of inhibitors of the clathrin pathway. Furthermore, we demonstrated that APLP2 and K d bind at the cell surface and are internalized together. The APLP2 cytoplasmic tail contains two overlapping consensus motifs for binding to the adaptor protein-2 complex, and mutation of a tyrosine shared by both motifs severely impaired APLP2 internalization and ability to promote K d endocytosis. Upon increased expression of wild type APLP2, K d molecules were predominantly directed to the lysosomes rather than recycled to the plasma membrane. These findings suggest a model in which APLP2 binds K d at the plasma membrane, facilitates uptake of K d in a clathrin-dependent manner, and routes the endocytosed K d to the lysosomal degradation pathway. Thus, APLP2 has a multistep trafficking function that influences the expression of major histocompatibility complex class I molecules at the plasma membrane.The efficacy of the cellular immune response to intracellular pathogens and tumors is reliant on major histocompatibility complex (MHC) 5 class I molecules. MHC class I molecules present peptides, including peptides derived from pathogens and tumors, at the cell surface to cytotoxic T lymphocytes.Cytotoxic T lymphocytes have been selected during development for their ability to react to cells in the periphery expressing self MHC class I molecules bearing non-self peptides. The level of cell surface expression of MHC class I molecules on infected and malignant cells therefore dictates the extent to which the antigen-specific cytotoxic T lymphocytes can recognize, and subsequently lyse, abnormal cells. The cell surface expression of MHC class I molecules is controlled by the quantity and quality of MHC class I molecules that are assembled, and also by the rate at which MHC class I molecules depart from the plasma membrane.Amyloid precursor-like protein 2 (APLP2) binds to the MHC class I molecule K d in cells that express ␤2-microglobulin (1, 2). APLP2 regulates the level of folded K d molecules at the cell surface: a reduction in APLP2 expression causes an elevation in the amount of folded K d at the plasma membrane, and an increase in APLP2 expression results in a decline in folded K d surface expression (3, 4). Higher APLP2 expression lowers the level of K d at the plasma membrane by increasing the endocytosis, destabilization, and turnover of K d molecules (4). The family of proteins to which APLP2 belongs includes APL-1 in Caenorhabditis elegans, APPL in Drosophila, and three proteins in mammals: amyloid precursor protein (APP), amyloid precursor-like protein 1, and APLP2 (5, 6). APLP2 shares a high degree of sequence homology with APP, particularly at the C-terminal end. However, ...

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Section: Discussionmentioning

confidence: 99%

Mechanism for Amyloid Precursor-like Protein 2 Enhancement of Major Histocompatibility Complex Class I Molecule Degradation

Tuli

Sharma

Capek

et al. 2009

Journal of Biological Chemistry

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“…6), expression of the ARF6-Q67L mutant, which blocks fusion of ARF6-positive endosomes with early endosomes, results in the accumulation of receptors in vacuole-like structures (49). The requirement for tyrosine-dependent endocytosis of Siglec-F has also been demonstrated for MHC-1 (42,63), although the exact role of this sequence in the endocytic mechanism remains to be defined.…”

Section: Discussionmentioning

confidence: 99%

Distinct Endocytic Mechanisms of CD22 (Siglec-2) and Siglec-F Reflect Roles in Cell Signaling and Innate Immunity

Tateno

Schur

et al. 2007

Molecular and Cellular Biology

116

109

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Sialic acid-binding immunoglobulin-like lectins (siglecs) are predominately expressed on immune cells. They are best known as regulators of cell signaling mediated by cytoplasmic tyrosine motifs and are increasingly recognized as receptors for pathogens that bear sialic acid-containing glycans. Most siglec proteins undergo endocytosis, an activity tied to their roles in cell signaling and innate immunity. Here, we investigate the endocytic pathways of two siglec proteins, CD22 (Siglec-2), a regulator of B-cell signaling, and mouse eosinophil Siglec-F, a member of the rapidly evolving CD33-related siglec subfamily that are expressed on cells of the innate immune system. CD22 exhibits hallmarks of clathrin-mediated endocytosis and traffics to recycling compartments, consistent with previous reports demonstrating its localization to clathrin domains. Like CD22, Siglec-F mediates endocytosis of anti-Siglec-F and sialoside ligands, a function requiring intact tyrosinebased motifs. In contrast, however, we find that Siglec-F endocytosis is clathrin and dynamin independent, requires ADP ribosylation factor 6, and traffics to lysosomes. The results suggest that these two siglec proteins have evolved distinct endocytic mechanisms consistent with roles in cell signaling and innate immunity.The siglec (sialic-acid binding immunoglobulin [Ig]-like lectins) proteins are subset of the Ig superfamily of cell recognition molecules that bind to sialic acid-containing glycans of cell surface glycoconjugates as ligands (27,78). Of the 13 human and 9 murine siglec proteins, 4 are highly conserved in mammalian species: sialoadhesin (Sn)/Siglec-1, CD22/Siglec-2, myelin-associated glycoprotein (MAG)/Siglec-4, and Siglec-15. The others comprise a rapidly evolving subfamily homologous to CD33/Siglec-4, known as the CD33-related siglec proteins. With two exceptions (MAG and Siglec-6) the siglec proteins are predominantly expressed in various white blood cells of the immune system (25,43,78,85). All contain a N-terminal V-set sugar-binding Ig domain, a variable number of additional C-set Ig domains, a transmembrane domain, and a cytoplasmic domain that typically contains tyrosine-based motifs implicated in regulation of cell signaling and endocytosis.Many of the siglec proteins contain one or more immunoreceptor tyrosine-based inhibitory motifs (ITIMs), (I/L/V)XYXX (L/V), suggesting that they play important roles as inhibitory receptors of cell signaling (25, 78), as exemplified by CD22, which is well documented as a regulator of B-cell receptor (BCR) signaling. Upon antigen binding to the BCR, the ITIMs of CD22 are quickly tyrosine phosphorylated and recruit protein tyrosine phosphatase SHP-1, which dephosphorylates the BCR and dampens the B-cell response, setting a threshold for B-cell activation (27,73).CD22 is also known to undergo endocytosis following ligation by anti-CD22 antibody (38, 64) or high-affinity multivalent-sialoside ligands (22). The tyrosine-based ITIMs of CD22 also fit the sorting signal YXXØ (where Ø is a hydrophobic...

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“…The amino acid epitopes recognized by these antibodies (HC-10, LA45, L31, M38 and HCA2) are indicated [7,8,10,12]. Also indicated are the specific amino acid sequences in the cytoplasmic tail proposed to regulate MHC-I endocytosis and intracellular trafficking [53,60,62].…”

Section: Mhc-i Molecules -Dynamic Structures With a Tendency To Open Upmentioning

confidence: 99%

Open conformers: the hidden face of MHC-I molecules

Arosa

Santos

Powis

2007

Trends in Immunology

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151

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Lack of Tyrosine 320 Impairs Spontaneous Endocytosis and Enhances Release of HLA-B27 Molecules

Cited by 26 publications

References 38 publications

Mechanism for Amyloid Precursor-like Protein 2 Enhancement of Major Histocompatibility Complex Class I Molecule Degradation

Mechanism for Amyloid Precursor-like Protein 2 Enhancement of Major Histocompatibility Complex Class I Molecule Degradation

Distinct Endocytic Mechanisms of CD22 (Siglec-2) and Siglec-F Reflect Roles in Cell Signaling and Innate Immunity

Open conformers: the hidden face of MHC-I molecules

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