Cell polarity is a common feature of eukaryotic cells. A polarized cell has a single axis of asymmetry, which can be thought of as “apical” and “basal” (illustrated in ) or “front” and “rear” (). This asymmetry encompasses a variety of cellular morphologies that can differ among cell types in a single organism, as well as within a single-celled organism such as Saccharomyces cerevisiae.
Cells within multicellular organisms also exhibit a distinct apical–basal axis of polarity. One example is epithelial initiation, which occurs during development and involves congression of mesenchymal cells into aggregates that differentiate to form polarized apical–basal cell monolayers. At the migratory stage, mesenchymal cells set up a front–rear axis of polarity (). These polarity principles contribute to the higher-order organization of cell-based systems, such as shaping the embryo, wiring the developing nervous system, maintaining and regenerating tissue, and developing the immune response (reviewed in Nelson, 2009
). Perturbations in cell polarity contribute to a number of tissue pathologies. Particularly striking examples include neuronal migration disorders (NMDs) such as schizencephaly, porencephaly, and lissencephaly, which are caused by defects in the polarized migration of neurons (for a review on NMDs, see Valiente and Marin, 2010
FIGURE 1: Comparison of cellular polarity in cytokinetic cells, polarized epithelial cells, and migrating cells. (A) In polarized cells the exocyst (orange) is required for basolateral secretory-vesicle delivery and apical endosomal membrane transport. The exocyst (more ...)
Specific sorting and maintenance of proteins to distinct membrane domains ensures polarity formation. The defined distribution of plasma membrane and cytoskeletal proteins in a polarized cell requires signaling networks and protein complexes comprising the Rho and Rab family GTPases, their downstream effectors, and polarity complexes (Crumbs, PAR, and Scribble). Effectors include cytoskeletal proteins and vesicle-trafficking pathways. Vesicle trafficking from the endocytic and/or exocytic membrane compartments along a polarized cytoskeleton network is required for the establishment of cellular polarity (reviewed in Nelson, 2009
). This has been elegantly illustrated in the budding yeast, S. cerevisiae
, in which bud growth is ensured by polarized secretion of Golgi apparatus–derived membrane vesicles to cortical actin patches under the regulation of Rho GTPases and polarity complexes at the bud tip (reviewed in Chant, 1999
; Irazoqui and Lew, 2004
). In multicellular eukaryotes, protein-sorting events occur at the endocytic pathway and Golgi apparatus to ensure cell polarization (Nelson, 2009
). For example, plasma membrane–endocytic recycling is critical for maintaining polarized membrane protein residency to establish appropriate responses to stimuli such as nutrient internalization, junctional protein sorting (e.g., E-cadherin), and ion channel recycling (Lock and Stow, 2005
; Ducharme et al., 2006
). Of interest, recent evidence shows that vesicle trafficking is also required for the establishment of polarized domains during cytokinesis, the final stage of cell division ().
Recent studies suggest that principles of cell polarity are engaged during the process of cytokinesis. For instance, a migrating polarized cell requires constant membrane addition via secretion at the leading edge to maintain “front–rear” polarity (Nelson, 2009
), just as abscission (the final stage of cytokinesis) requires membrane addition at the cytokinetic bridge via secretion and endocytic vesicle delivery (further discussed in the review by Prekeris and Gould, 2008
, and depicted in ). In both cases, membrane vesicles may act as a platform for delivering essential regulators ensuring cell polarization. Another similarity between cell polarity and cytokinesis occurs within S. cerevisiae.
In G1/S an actin patch is focused at the bud tip where secretory vesicles are directed, and then the patch dissipates as the bud becomes larger and the cell enters cytokinesis. Prior to spindle disassembly and cell separation, polarized-actin patch proteins and secretory vesicles are redirected to the mother bud neck, a structure analogous to the cytokinetic bridge (VerPlank and Li, 2005
). The apparent importance of polarized vesicle trafficking to polarity and the final stages of cytokinesis leads one to speculate about a conserved underlying mechanism between the two processes. This notion will be discussed and proposed throughout this essay.
FIGURE 2: Polarized membrane trafficking and membrane fusion at the midbody during abscission. Secretory vesicles (green) and Rab11-decorated endocytic recycling membranes (pink) undergo directed motility to the cytokinetic bridge. However, the temporal relationship (more ...)