Compartmentalization of Aquaporins in the Human Intestine

Hari H P Cohly,Raphael Isokpehi,Rajendram V Rajnarayanan

doi:10.3390/ijerph5020115

Abstract

Improper localization of water channel proteins called aquaporins (AQP) induce mucosal injury which is implicated in Crohn's disease and ulcerative colitis. The amino acid sequences of AQP3 and AQP10 are 79% similar and belong to the mammalian aquaglyceroporin subfamily. AQP10 is localized on the apical compartment of the intestinal epithelium called the glycocalyx while AQP3 is selectively targeted to the basolateral membrane. Despite the high sequence similarity and evolutionary relatedness, the molecular mechanism involved in the polarity, selective targeting and function of AQP3 and AQP10 in the intestine is largely unknown. Our hypothesis is that the differential polarity and selective targeting of AQP3 and AQP10 in the intestinal epithelial cells is influenced by amino acid signal motifs. We performed sequence and structural alignments to determine differences in signals for localization and posttranslational glycosylation. The basolateral sorting motif "YRLL" is present in AQP3 but absent in AQP10; while Nglycosylation signals are present in AQP10 but absent in AQP3. Furthermore, the C-terminal region of AQP3 is longer compared to AQP10. The sequence and structural differences between AQP3 and AQP10 provide insights into the differential compartmentalization and function of these two aquaporins commonly expressed in human intestines.

Highlights

Aquaporins (AQPs) are cell surface proteins that provide selective and rapid transport of water across the cell membrane [1]
Alterations in fluid flux can result in disease conditions such as ulcerative colitis and Crohn’s disease as a consequence of mucosal injury [3,6]
AQP10 is localized on the apical compartment of the intestinal epithelium called the glycocalyx while AQP3 is selectively targeted to the basolateral membrane [16]

Summary

Introduction

Aquaporins (AQPs) are cell surface proteins that provide selective and rapid transport of water across the cell membrane [1]. Most cell surface proteins contain signals within their cytoplasmic termini that permit their recruitment into endocytic vesicles, which in turn facilitates their selective compartmentalization in the apical or basolateral membranes selectively [7, 8]. Class II: The di-leucine motif (LL) is another well known endocytosis motif that is present within many transmembrane cell surface proteins [11]. AQP10 is localized on the apical compartment of the intestinal epithelium called the glycocalyx while AQP3 is selectively targeted to the basolateral membrane [16]. Our hypothesis is that the differential polarity and selective targeting of AQP3 and AQP10 in the intestinal epithelial cells is influenced by amino acid signal motifs. We performed sequence and structural alignments to determine differences in signals for localization and post-translational glycosylation. It is of interest to decipher the significance in the structural and sequence differences between AQP3 and AQP10

Methods

Results and Discussion

Conclusion