Location of the Cell Adhesion Molecule "Coxsackievirus and Adenovirus Receptor" in the Adult Mouse Brain.

Amani Wehbi,Iria G Dopeso-Reyes,Eric J Kremer

doi:10.3389/fnana.2020.00028

Abstract

The coxsackievirus and adenovirus receptor (CAR) is a single-pass transmembrane cell adhesion molecule (CAM). CAR is expressed in numerous mammalian tissues including the brain, heart, lung, and testes. In epithelial cells, CAR functions are typical of the quintessential roles of numerous CAMs. However, in the brain the multiple roles of CAR are poorly understood. To better understand the physiological role of CAR in the adult brain, characterizing its location is a primordial step to advance our knowledge of its functions. In addition, CAR is responsible for the attachment, internalization, and retrograde transport of canine adenovirus type 2 (CAV-2) vectors, which have found a niche in the mapping of neuronal circuits and gene transfer to treat and model neurodegenerative diseases. In this study, we used immunohistochemistry and immunofluorescence to document the global location of CAR in the healthy, young adult mouse brain. Globally, we found that CAR is expressed by maturing and mature neurons in the brain parenchyma and located on the soma and on projections. While CAR occasionally colocalizes with glial fibrillary acidic protein, this overlap was restricted to areas that are associated with adult neurogenesis.

Highlights

Cell adhesion molecules (CAMs) are multifunctional proteins that, as the name suggests, mediate interactions between cells or between cells and the extracellular matrix (ECM)
coxsackievirus and adenovirus receptor (CAR) immunoreactivity was readily detected in the cortex, olfactory bulb, striatum, septum, amygdala, hippocampus, some areas of the thalamus and hypothalamus, superior colliculus, and the brainstem
We found a population of CARimmunoreactive cells located in the caudal region of the 4th ventricle, area postrema, with the somas situated in the ventricular zone and the projections toward the parenchyma (Figures 7J,L)

Summary

Introduction

Cell adhesion molecules (CAMs) are multifunctional proteins that, as the name suggests, mediate interactions between cells or between cells and the extracellular matrix (ECM) (reviewed by Cavallaro and Dejana, 2011). The coxsackievirus and adenovirus receptor (CAR) belongs to the cortical thymocyte marker in xenopus CTX subfamily of IgCAMs (Chrétien et al, 1998; reviewed by Loustalot et al, 2016). CAR has the classical structure of IgCAMs: the extracellular domain (ECD) is composed of two Ig-like domains (D1 and D2) followed by a single-pass transmembrane domain (TM) and an intracellular domain (ICD) (Loustalot et al, 2016). The ECD and ICD of CAR interact with numerous intracellular and extracellular proteins (ibid). CAR is widely expressed in tight junction in the epithelial tissue in the adult mouse gastrointestinal tract, respiratory tract, kidney, and male reproductive system; it is present in the liver, lymphatic system, skeletal muscle, and myocardial cells (Cohen et al, 2001; Shaw et al, 2004; Raschperger et al, 2006)

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Results

Conclusion