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

Joseph G Skeate,Varsha D Samararatne,Julia R Taylor,Shantae M Thornton,Christopher Buser,Diane M Da Silva,W Martin Kast,Kim P Lühen

doi:10.3390/cells9040974

Joseph G Skeate, Varsha D Samararatne + Show 6 more

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https://doi.org/10.3390/cells9040974

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Abstract

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.

Highlights

Birbeck granules (BG) are cytoplasmic organelles which resemble tennis rackets in two-dimensional (2D) cross-sections
We previously reported that this manipulation of Langerhans cells (LC) by human papillomavirus (HPV) is facilitated by the interaction with the annexin A2 S100A10 heterotetramer (A2t) [20]
We found that overall langerin expression was decreased with annexin A2 (anxA2) knockdown MUTZ-3-derived LC (M-LC) as compared with wild type (WT) M-LC (Figure 3C)

Summary

Introduction

Birbeck granules (BG) are cytoplasmic organelles which resemble tennis rackets in two-dimensional (2D) cross-sections. Since their discovery nearly 60 years ago, BG have largely remained elusive in derivation, composition, and function [1]. Collective evidence has demonstrated a function for langerin and BG in antigen binding, uptake, and processing through a nonclassical pathway [9,10,11,12].

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