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Drosophila melanogaster Cad99C, the orthologue of human Usher cadherin PCDH15, regulates the length of microvilli.

D'Alterio C, Tran DD, Yeung MW, Hwang MS, Li MA, Arana CJ, Mulligan VK, Kubesh M, Sharma P, Chase M, Tepass U, Godt D - J. Cell Biol. (2005)

Bottom Line: Loss of Cad99C function results in shortened and disorganized microvilli, whereas overexpression of Cad99C leads to a dramatic increase of microvillus length.Cad99C that lacks most of the cytoplasmic domain, including potential PDZ domain-binding sites, still promotes excessive microvillus outgrowth, suggesting that the amount of the extracellular domain determines microvillus length.This study reveals Cad99C as a critical regulator of microvillus length, the first example of a transmembrane protein that is involved in this process.

View Article: PubMed Central - PubMed

Affiliation: Department of Zoology, University of Toronto, Toronto, Ontario, Canada, M5S 3G5.

ABSTRACT
Actin-based protrusions can form prominent structures on the apical surface of epithelial cells, such as microvilli. Several cytoplasmic factors have been identified that control the dynamics of actin filaments in microvilli. However, it remains unclear whether the plasma membrane participates actively in microvillus formation. In this paper, we analyze the function of Drosophila melanogaster cadherin Cad99C in the microvilli of ovarian follicle cells. Cad99C contributes to eggshell formation and female fertility and is expressed in follicle cells, which produce the eggshells. Cad99C specifically localizes to apical microvilli. Loss of Cad99C function results in shortened and disorganized microvilli, whereas overexpression of Cad99C leads to a dramatic increase of microvillus length. Cad99C that lacks most of the cytoplasmic domain, including potential PDZ domain-binding sites, still promotes excessive microvillus outgrowth, suggesting that the amount of the extracellular domain determines microvillus length. This study reveals Cad99C as a critical regulator of microvillus length, the first example of a transmembrane protein that is involved in this process.

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Function of Cad99C: summary and model. (A) Cad99C is located in apical microvilli of ovarian follicle cells. (B) The length of microvilli depends on the expression level of Cad99C. (C) Model 1 shows that the CDs of Cad99C (red) interact with an extracellular ligand (blue), which stabilizes the membrane or influences the dynamics of the actin bundle of the microvillus. Model 2 shows that the CDs of Cad99C assemble into a scaffold, stabilizing the microvillus membrane.
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fig7: Function of Cad99C: summary and model. (A) Cad99C is located in apical microvilli of ovarian follicle cells. (B) The length of microvilli depends on the expression level of Cad99C. (C) Model 1 shows that the CDs of Cad99C (red) interact with an extracellular ligand (blue), which stabilizes the membrane or influences the dynamics of the actin bundle of the microvillus. Model 2 shows that the CDs of Cad99C assemble into a scaffold, stabilizing the microvillus membrane.

Mentions: Our study shows that the loss of Cad99C results in shorter microvilli and overexpression in longer microvilli than in wild type (Fig. 7, A and B), indicating that the concentration of Cad99C is positively correlated with the length of microvilli in follicle cells. Interestingly, modifications in the Cad99C mRNA expression level during oogenesis appear to be good indicators for changes in microvilli. During mid-oogenesis, prominent expression of Cad99C is seen in follicle cells that show forming and growing apical microvilli (Fig. 1, A, G, and H; Fig. 4 G; and not depicted), and Cad99C expression culminates when microvilli reach their maximum extension (Fig. 1 B and Fig. 4 H). The following drop of mRNA levels in most follicle cells coincides with a regression of microvillus size (Fig. 1 C and Fig. 4, I and J), whereas centripetal cells express Cad99C strongly (Fig. 1 C), consistent with the delayed formation of a microvillus brush border by these follicle cells (Mahowald and Kambysellis, 1980; unpublished data). We therefore propose that transcriptionally regulated changes in the concentration of Cad99C are critically involved in the dynamic remodeling of follicle cell microvilli.


Drosophila melanogaster Cad99C, the orthologue of human Usher cadherin PCDH15, regulates the length of microvilli.

D'Alterio C, Tran DD, Yeung MW, Hwang MS, Li MA, Arana CJ, Mulligan VK, Kubesh M, Sharma P, Chase M, Tepass U, Godt D - J. Cell Biol. (2005)

Function of Cad99C: summary and model. (A) Cad99C is located in apical microvilli of ovarian follicle cells. (B) The length of microvilli depends on the expression level of Cad99C. (C) Model 1 shows that the CDs of Cad99C (red) interact with an extracellular ligand (blue), which stabilizes the membrane or influences the dynamics of the actin bundle of the microvillus. Model 2 shows that the CDs of Cad99C assemble into a scaffold, stabilizing the microvillus membrane.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2171266&req=5

fig7: Function of Cad99C: summary and model. (A) Cad99C is located in apical microvilli of ovarian follicle cells. (B) The length of microvilli depends on the expression level of Cad99C. (C) Model 1 shows that the CDs of Cad99C (red) interact with an extracellular ligand (blue), which stabilizes the membrane or influences the dynamics of the actin bundle of the microvillus. Model 2 shows that the CDs of Cad99C assemble into a scaffold, stabilizing the microvillus membrane.
Mentions: Our study shows that the loss of Cad99C results in shorter microvilli and overexpression in longer microvilli than in wild type (Fig. 7, A and B), indicating that the concentration of Cad99C is positively correlated with the length of microvilli in follicle cells. Interestingly, modifications in the Cad99C mRNA expression level during oogenesis appear to be good indicators for changes in microvilli. During mid-oogenesis, prominent expression of Cad99C is seen in follicle cells that show forming and growing apical microvilli (Fig. 1, A, G, and H; Fig. 4 G; and not depicted), and Cad99C expression culminates when microvilli reach their maximum extension (Fig. 1 B and Fig. 4 H). The following drop of mRNA levels in most follicle cells coincides with a regression of microvillus size (Fig. 1 C and Fig. 4, I and J), whereas centripetal cells express Cad99C strongly (Fig. 1 C), consistent with the delayed formation of a microvillus brush border by these follicle cells (Mahowald and Kambysellis, 1980; unpublished data). We therefore propose that transcriptionally regulated changes in the concentration of Cad99C are critically involved in the dynamic remodeling of follicle cell microvilli.

Bottom Line: Loss of Cad99C function results in shortened and disorganized microvilli, whereas overexpression of Cad99C leads to a dramatic increase of microvillus length.Cad99C that lacks most of the cytoplasmic domain, including potential PDZ domain-binding sites, still promotes excessive microvillus outgrowth, suggesting that the amount of the extracellular domain determines microvillus length.This study reveals Cad99C as a critical regulator of microvillus length, the first example of a transmembrane protein that is involved in this process.

View Article: PubMed Central - PubMed

Affiliation: Department of Zoology, University of Toronto, Toronto, Ontario, Canada, M5S 3G5.

ABSTRACT
Actin-based protrusions can form prominent structures on the apical surface of epithelial cells, such as microvilli. Several cytoplasmic factors have been identified that control the dynamics of actin filaments in microvilli. However, it remains unclear whether the plasma membrane participates actively in microvillus formation. In this paper, we analyze the function of Drosophila melanogaster cadherin Cad99C in the microvilli of ovarian follicle cells. Cad99C contributes to eggshell formation and female fertility and is expressed in follicle cells, which produce the eggshells. Cad99C specifically localizes to apical microvilli. Loss of Cad99C function results in shortened and disorganized microvilli, whereas overexpression of Cad99C leads to a dramatic increase of microvillus length. Cad99C that lacks most of the cytoplasmic domain, including potential PDZ domain-binding sites, still promotes excessive microvillus outgrowth, suggesting that the amount of the extracellular domain determines microvillus length. This study reveals Cad99C as a critical regulator of microvillus length, the first example of a transmembrane protein that is involved in this process.

Show MeSH
Related in: MedlinePlus