Junctional trafficking and epithelial morphogenesis
Introduction
Epithelial monolayers are major determinants of tissue structure that provide the basis for many aspects of tissue morphogenesis. The remodeling of epithelial tissues drives fundamental morphogenetic changes including elongation of the body axis [1, 2], branching of the lung [3, 4], and closure of the neural tube [5, 6]. Epithelial tissues are characterized by strong intercellular adhesion that would seem to present a barrier to cell rearrangement. The primary mechanism of adhesion in developing epithelia is the trans-dimerization of E-cadherin molecules on adjacent cell surfaces, which assemble into junctional complexes through the association of the E-cadherin intracellular domain with β-catenin and α-catenin. Recent studies demonstrate that adherens junctions are continually turned over through the cellular vesicle transport machinery [7, 8, 9], a mechanism that could facilitate the dynamic reorganization of cell interactions during processes of cell division, cell death, and cell rearrangement. Here we focus on recent studies in Drosophila, where this unexpectedly dynamic process is required for stable adhesion as well as for cell polarity and rearrangement during epithelial morphogenesis.
Section snippets
E-cadherin trafficking promotes adhesion in stable epithelia
The cellular vesicle transport machinery delivers E-cadherin and other transmembrane proteins from sites of protein synthesis in the endoplasmic reticulum to specific destinations at the cell surface [10]. Vesicle trafficking can also remove E-cadherin from the plasma membrane by endocytosis [7, 8, 9]. The internalization of surface E-cadherin into early endosomes requires the vesicle scission factor dynamin and the Rab5 GTPase. E-cadherin in the early endosomes is then routed either to the
Emerging roles for E-cadherin trafficking in cell rearrangement
While membrane trafficking has primarily been characterized for its role in promoting adhesion in nonmoving cells, there are hints that junctional trafficking may also play an active role in cell rearrangement. The prepupal Drosophila wing disc is a highly disordered epithelium, with each cell contacting a variable number of neighbors. During pupal development this epithelium reorganizes to produce a more regular hexagonal lattice through the local remodeling of adherens junctions [41••].
Dynamic association between adherens junctions and the cytoskeleton
Adherens junctions are stabilized by several mechanisms in addition to protein trafficking, including the clustering of E-cadherin into adhesive microdomains and interactions with the actin cytoskeleton [45, 46]. When epithelial cells first make contact in culture, E-cadherin accumulates in punctate microdomains at the contact site [47, 48] along with a burst of F-actin that has been observed both in culture [49] and in vivo [50••]. FRAP and GFP tracking experiments in culture demonstrate that
Conclusions
A common theme emerging from in vivo studies of adherens junction regulation is that adherens junction proteins are dynamically turned over at the cell surface, even in epithelial tissues where adhesion is stable. Paradoxically, junctional turnover often appears to promote adhesion, as both endocytosis and exocytosis are necessary to maintain stable adhesion between cells in several Drosophila epithelia [12••, 13••, 14••, 15••, 16••]. How does the trafficking of junctional proteins contribute
References and recommended reading
Papers of particular interest, published within the period of review, have been highlighted as:
• of special interest
•• of outstanding interest
Acknowledgments
We are grateful to Buzz Baum and members of the Zallen lab for comments on the manuscript, and Richard Zallen for suggestions on Figure 1. FWP is supported by a long-term fellowship of the Human Frontiers Science Program. JAZ is supported by a Burroughs Wellcome Career Award in the Biomedical Sciences, a Searle Scholar award, a WM Keck Foundation Distinguished Young Scholar in Medical Research award, and NIH/NIGMS R01 GM079340.
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