The cytoskeleton in development of epithelial cell polarity

Abstract

SUMMARYThe polarization of intestinal epithelial cells and the stereotypic arrangement of their actin-based cytoskel eton have made these epithelia an excellent system to explore the organization and formation of a cortical actin-based cytoskeleton. Through a combined morpho logical and biochemical analysis, the molecular arrange ment of many of the components of the brush border has been elucidated. Study of brush border assembly in the Crypts of Lieberkiihn suggests that cytoskeletal mRNA and protein expression, as well as morphologi cal development, occur rapidly following cell differen tiation. Protein kinases appear to be important regula tors of intestinal cell growth, for differentiating cells in the crypts possess 15-fold higher levels of tyrosine phosphorylated proteins than differentiated cells of the villus. One of these kinases, pp60c'5Te, has a 4-to 7-fold higher activity in crypts and increased association with the cytoskeleton than it has in villus cells.The development and maintenance of polarization in epithelial cells require the targeting and transport of specific proteins to the apical and basolateral plasma membrane. It has been proposed that a dynein-like, microtubule-based motor is involved in the transport of apically directed materials from the tram-Golgi to the apical plasma membrane. However, microtubules do not reach the plasma membrane, but terminate below the actin-rich network of filaments comprising the terminal web. We propose that vesicles translocate from the Golgi to the apical cytoplasm along microtubules using dynein, and then move through the terminal web to reach the apical plasma membrane using the actin-based motor myosin-I. Our isolation of Golgi-derived vesicles pos sessing both myosin-I and dynein on their cytoplasmic surface is consistent with this hypothesis.

Class I Myosins Have Overlapping and Specialized Functions in Left-Right Asymmetric Development inDrosophila

“…Myo31DF and Myo61F are both known to be present in the apical brush border of the larval midgut enterocyte (Morgan et al 1995). The apical brush border is composed of microvilli supported by F-actin bundles that protrude into the terminal web domain (Fath et al 1993;Phillips and Thomas 2006) (Figure 5D). Protein delivery and recovery by endocytosis and exocytosis actively occur in the microvilli.…”

Cortactin: coupling membrane dynamics to cortical actin assembly

“…In addition, they establish a di usion barrier for integral membrane proteins within individual cells by dividing the plasma membrane into apical and basolateral domains (Tsukita et al, 1999). Tight junctions are associated with an apical cytoskeletal structure known as the terminal web (Fath et al, 1993). Cortactin is localized at the terminal web in human small bowel epithelium (Wu and Montone, 1998) and the SH3 domain associates with a proline-rich motif in ZO-1 (Katsube et al, 1998), a protein selectively localized to the epithelial tight junction (Stevenson et al, 1986).…”

Intermediate filaments: A role in epithelial polarity

“…A thick layer of IFs lies immediately below and within the terminal web, at the rootlets of the microvilli [23]. Only thin, isolated bundles of IFs extend along the apical-most half of the lateral domain (Fig.…”