The Essential Role of anxA2 in Langerhans Cell Birbeck Granules Formation. 2020

Shantae M Thornton, and Varsha D Samararatne, and Joseph G Skeate, and Christopher Buser, and Kim P Lühen, and Julia R Taylor, and Diane M Da Silva, and W Martin Kast
Department of Molecular Microbiology and Immunology, University of Southern California, Los Angeles, CA 90033, USA.

Langerhans cells (LC) are the resident antigen presenting cells of the mucosal epithelium and play an essential role in initiating immune responses. LC are the only cells in the body to contain Birbeck granules (BG), which are unique cytoplasmic organelles comprised of c-type lectin langerin. Studies of BG have historically focused on morphological characterizations, but BG have also been implicated in viral antigen processing which suggests that they can serve a function in antiviral immunity. This study focused on investigating proteins that could be involved in BG formation to further characterize their structure using transmission electron microscopy (TEM). Here, we report a critical role for the protein annexin A2 (anxA2) in the proper formation of BG structures. When anxA2 expression is downregulated, langerin expression decreases, cytoplasmic BG are nearly ablated, and the presence of malformed BG-like structures increases. Furthermore, in the absence of anxA2, we found langerin was no longer localized to BG or BG-like structures. Taken together, these results indicate an essential role for anxA2 in facilitating the proper formation of BG.

UI MeSH Term Description Entries
D007801 Langerhans Cells Recirculating, dendritic, antigen-presenting cells containing characteristic racket-shaped granules (Birbeck granules). They are found principally in the stratum spinosum of the EPIDERMIS and are rich in Class II MAJOR HISTOCOMPATIBILITY COMPLEX molecules. Langerhans cells were the first dendritic cell to be described and have been a model of study for other dendritic cells (DCs), especially other migrating DCs such as dermal DCs and INTERSTITIAL DENDRITIC CELLS. Langerhans Cell,Dendritic Cells, Dermal,Dendritic Cells, Epidermal,Dendritic Cells, Skin,Dermal Dendritic Cells,Epidermal Dendritic Cells,Skin Dendritic Cells,Cell, Dermal Dendritic,Cell, Epidermal Dendritic,Cell, Langerhans,Cell, Skin Dendritic,Cells, Dermal Dendritic,Cells, Epidermal Dendritic,Cells, Langerhans,Cells, Skin Dendritic,Dendritic Cell, Dermal,Dendritic Cell, Epidermal,Dendritic Cell, Skin,Dermal Dendritic Cell,Epidermal Dendritic Cell,Skin Dendritic Cell
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D003594 Cytoplasmic Granules Condensed areas of cellular material that may be bounded by a membrane. Cytoplasmic Granule,Granule, Cytoplasmic,Granules, Cytoplasmic
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D015703 Antigens, CD Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation. CD Antigen,Cluster of Differentiation Antigen,Cluster of Differentiation Marker,Differentiation Antigens, Leukocyte, Human,Leukocyte Differentiation Antigens, Human,Cluster of Differentiation Antigens,Cluster of Differentiation Markers,Antigen Cluster, Differentiation,Antigen, CD,CD Antigens,Differentiation Antigen Cluster,Differentiation Marker Cluster,Marker Cluster, Differentiation
D017306 Annexin A2 A member of the annexin family that is a substrate for a tyrosine kinase, ONCOGENE PROTEIN PP60(V-SRC). Annexin A2 occurs as a 36-KDa monomer and in a 90-KDa complex containing two subunits of annexin A2 and two subunits of S100 FAMILY PROTEIN P11. The monomeric form of annexin A2 was formerly referred to as calpactin I heavy chain. Annexin II,Calpactin I,Lipocortin II,Annexin A2, P90 Complex,Annexin II, P36,Annexin II, P90 Complex,Capactin I Heavy Chain,P36 Annexin II
D021122 Protein Subunits Single chains of amino acids that are the units of multimeric PROTEINS. Multimeric proteins can be composed of identical or non-identical subunits. One or more monomeric subunits may compose a protomer which itself is a subunit structure of a larger assembly. Protomers,Protein Subunit,Protomer,Subunit, Protein,Subunits, Protein
D021381 Protein Transport The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport. Cellular Protein Targeting,Gated Protein Transport,Protein Targeting, Cellular,Protein Translocation,Transmembrane Protein Transport,Vesicular Protein Transport,Protein Localization Processes, Cellular,Protein Sorting,Protein Trafficking,Protein Transport, Gated,Protein Transport, Transmembrane,Protein Transport, Vesicular,Traffickings, Protein
D037181 Lectins, C-Type A class of animal lectins that bind to carbohydrate in a calcium-dependent manner. They share a common carbohydrate-binding domain that is structurally distinct from other classes of lectins. C-Type Lectin Receptor,C-Type Lectins,C-Type Lectin,Lectin, C-Type,Receptors, C-Type Lectin,C Type Lectin,C Type Lectin Receptor,C Type Lectins,C-Type Lectin Receptors,Lectin Receptor, C-Type,Lectin Receptors, C-Type,Lectin, C Type,Lectins, C Type,Receptor, C-Type Lectin,Receptors, C Type Lectin
D037241 Mannose-Binding Lectins A subclass of lectins that are specific for CARBOHYDRATES that contain MANNOSE. Mannose-Specific Lectin,Lectin, Mannose-Specific,Lectins, Mannose-Binding,Mannose Binding Lectins,Mannose Specific Lectin

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