Limits...
Growth control by EGF repeats of the C. elegans Fibulin-1C isoform.

Hesselson D, Kimble J - J. Cell Biol. (2006)

Bottom Line: Curr.Development. 132: 4223-4234).

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics, University of Wisconsin-Madison, Madison, WI 53706, USA.

ABSTRACT
Fibulin is a broadly conserved component of the extracellular matrix (ECM). Previous studies have shown that Caenorhabditis elegans FIBULIN-1 (FBL-1) controls the width of the gonad (Hesselson, D., C. Newman, K.W. Kim, and J. Kimble. 2004. Curr. Biol. 14:2005-2010; Kubota, Y., R. Kuroki, and K. Nishiwaki. 2004. Curr. Biol. 14:2011-2018; Muriel, J.M., C. Dong, H. Hutter, and B.E. Vogel. 2005. Development. 132: 4223-4234). In this study, we report that FBL-1 also controls developmental growth and that one isoform of fibulin-1, called FBL-1C, controls both functions by distinct mechanisms. A large FBL-1C fragment, including both epidermal growth factor (EGF) and fibulin-type C domains, is responsible for constraining gonadal width, but a much smaller fragment containing only two complete EGF repeats (EGF1-2C+) is critical for developmental growth. We suggest that the larger fragment serves a scaffolding function to stabilize the basement membrane and that the smaller fragment provides a regulatory function at the cell surface or within the ECM to control growth.

Show MeSH

Related in: MedlinePlus

A fbl-1  allele. (A, top) fbl-1 gene modified from Muriel et al. (2005). Alternative splicing of exons C and D generates FBL-1C and -1D. (bottom) FBL-1C and -1D proteins. (B) Duration of larval development, measured in hours from L1 to mid-L4. n = 25. (C) Adult body size measured in micrometers squared. n = 10. (B and C) Data are given as the mean ± SEM (error bars). (D–F) Mid-L4 larvae; genotypes are given in the figure. Lines indicate the gonadal width. Arrowheads point to the distal ends of gonads. Bars, 20 μm.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC1747532&req=5

fig1: A fbl-1 allele. (A, top) fbl-1 gene modified from Muriel et al. (2005). Alternative splicing of exons C and D generates FBL-1C and -1D. (bottom) FBL-1C and -1D proteins. (B) Duration of larval development, measured in hours from L1 to mid-L4. n = 25. (C) Adult body size measured in micrometers squared. n = 10. (B and C) Data are given as the mean ± SEM (error bars). (D–F) Mid-L4 larvae; genotypes are given in the figure. Lines indicate the gonadal width. Arrowheads point to the distal ends of gonads. Bars, 20 μm.

Mentions: The Caenorhabditis elegans FIBULIN-1 (FBL-1) protein is homologous to mammalian Fibulin-1 (Barth et al., 1998). Both proteins share a common domain architecture with an N-terminal signal sequence, three anaphylatoxin (AT) repeats, nine EGF-like repeats, and an alternatively spliced fibulin-type (FIB) C-terminal domain (Fig. 1 A). The AT domain is related to inflammatory peptides that are released during activation of the complement system (Kohl, 2001). EGF-like repeats often mediate protein–protein interactions and can function as signaling ligands (Prigent and Lemoine, 1992). The mammalian Fibulin-1 EGF domain is required for binding to other basement membrane proteins, including nidogen-1 and fibronectin (Sasaki et al., 1995; Tran et al., 1997). In C. elegans, the second EGF repeat is alternatively spliced, generating a choice between a canonical EGF repeat (EGF2C) and a divergent EGF repeat (EGF2D) with a 39-aa insertion. The FIB domain defines the fibulin family of proteins, which includes five proteins in mammals but only FBL-1 in C. elegans. Mammalian and nematode Fibulin-1 homologues share the C and D alternatively spliced FIB domains (Barth et al., 1998). The FIB domain may control the specificity of physical interactions because mammalian Fibulin-1C has a 30-fold higher affinity than Fibulin-1D for nidogen-1 (Sasaki et al., 1995).


Growth control by EGF repeats of the C. elegans Fibulin-1C isoform.

Hesselson D, Kimble J - J. Cell Biol. (2006)

A fbl-1  allele. (A, top) fbl-1 gene modified from Muriel et al. (2005). Alternative splicing of exons C and D generates FBL-1C and -1D. (bottom) FBL-1C and -1D proteins. (B) Duration of larval development, measured in hours from L1 to mid-L4. n = 25. (C) Adult body size measured in micrometers squared. n = 10. (B and C) Data are given as the mean ± SEM (error bars). (D–F) Mid-L4 larvae; genotypes are given in the figure. Lines indicate the gonadal width. Arrowheads point to the distal ends of gonads. Bars, 20 μm.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1747532&req=5

fig1: A fbl-1 allele. (A, top) fbl-1 gene modified from Muriel et al. (2005). Alternative splicing of exons C and D generates FBL-1C and -1D. (bottom) FBL-1C and -1D proteins. (B) Duration of larval development, measured in hours from L1 to mid-L4. n = 25. (C) Adult body size measured in micrometers squared. n = 10. (B and C) Data are given as the mean ± SEM (error bars). (D–F) Mid-L4 larvae; genotypes are given in the figure. Lines indicate the gonadal width. Arrowheads point to the distal ends of gonads. Bars, 20 μm.
Mentions: The Caenorhabditis elegans FIBULIN-1 (FBL-1) protein is homologous to mammalian Fibulin-1 (Barth et al., 1998). Both proteins share a common domain architecture with an N-terminal signal sequence, three anaphylatoxin (AT) repeats, nine EGF-like repeats, and an alternatively spliced fibulin-type (FIB) C-terminal domain (Fig. 1 A). The AT domain is related to inflammatory peptides that are released during activation of the complement system (Kohl, 2001). EGF-like repeats often mediate protein–protein interactions and can function as signaling ligands (Prigent and Lemoine, 1992). The mammalian Fibulin-1 EGF domain is required for binding to other basement membrane proteins, including nidogen-1 and fibronectin (Sasaki et al., 1995; Tran et al., 1997). In C. elegans, the second EGF repeat is alternatively spliced, generating a choice between a canonical EGF repeat (EGF2C) and a divergent EGF repeat (EGF2D) with a 39-aa insertion. The FIB domain defines the fibulin family of proteins, which includes five proteins in mammals but only FBL-1 in C. elegans. Mammalian and nematode Fibulin-1 homologues share the C and D alternatively spliced FIB domains (Barth et al., 1998). The FIB domain may control the specificity of physical interactions because mammalian Fibulin-1C has a 30-fold higher affinity than Fibulin-1D for nidogen-1 (Sasaki et al., 1995).

Bottom Line: Curr.Development. 132: 4223-4234).

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics, University of Wisconsin-Madison, Madison, WI 53706, USA.

ABSTRACT
Fibulin is a broadly conserved component of the extracellular matrix (ECM). Previous studies have shown that Caenorhabditis elegans FIBULIN-1 (FBL-1) controls the width of the gonad (Hesselson, D., C. Newman, K.W. Kim, and J. Kimble. 2004. Curr. Biol. 14:2005-2010; Kubota, Y., R. Kuroki, and K. Nishiwaki. 2004. Curr. Biol. 14:2011-2018; Muriel, J.M., C. Dong, H. Hutter, and B.E. Vogel. 2005. Development. 132: 4223-4234). In this study, we report that FBL-1 also controls developmental growth and that one isoform of fibulin-1, called FBL-1C, controls both functions by distinct mechanisms. A large FBL-1C fragment, including both epidermal growth factor (EGF) and fibulin-type C domains, is responsible for constraining gonadal width, but a much smaller fragment containing only two complete EGF repeats (EGF1-2C+) is critical for developmental growth. We suggest that the larger fragment serves a scaffolding function to stabilize the basement membrane and that the smaller fragment provides a regulatory function at the cell surface or within the ECM to control growth.

Show MeSH
Related in: MedlinePlus