Loss of C. elegans BBS-7 and BBS-8 protein function results in cilia defects and compromised intraflagellar transport

Oliver E. Blacque; Michael J. Reardon; Chunmei Li; Jonathan McCarthy; Moe R. Mahjoub; Stephen J. Ansley; Jose L. Badano; Allan K. Mah; Philip L. Beales; William S. Davidson; Robert C. Johnsen; Mark Audeh; Ronald H.A. Plasterk; David L. Baillie; Nicholas Katsanis; Lynne M. Quarmby; Stephen R. Wicks; Michel R. Leroux

doi:10.1101/gad.1194004

Loss of C. elegans BBS-7 and BBS-8 protein function results in cilia defects and compromised intraflagellar transport

Oliver E. Blacque, Michael J. Reardon, Chunmei Li, Jonathan McCarthy, Moe R. Mahjoub, Stephen J. Ansley, Jose L. Badano, Allan K. Mah, Philip L. Beales, William S. Davidson, Robert C. Johnsen, Mark Audeh, Ronald H.A. Plasterk, David L. Baillie, Nicholas Katsanis, Lynne M. Quarmby, Stephen R. Wicks, Michel R. Leroux

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298 Scopus citations

Abstract

Bardet-Biedl syndrome (BBS) is a genetically heterogeneous developmental disorder whose molecular basis is largely unknown. Here, we show that mutations in the Caenorhabditis elegans bbs-7 and bbs-8 genes cause structural and functional defects in cilia. C. elegans BBS proteins localize predominantly at the base of cilia, and like proteins involved in intraflagellar transport (IFT), a process necessary for cilia biogenesis and maintenance, move bidirectionally along the ciliary axoneme. Importantly, we demonstrate that BBS-7 and BBS-8 are required for the normal localization/motility of the IFT proteins OSM-5/Polaris and CHE-11, and to a notably lesser extent, CHE-2. We propose that BBS proteins play important, selective roles in the assembly and/or function of IFT particle components. Our findings also suggest that some of the cardinal and secondary symptoms of BBS, such as obesity, diabetes, cardiomyopathy, and learning defects may result from cilia dysfunction.

Original language	English
Pages (from-to)	1630-1642
Number of pages	13
Journal	Genes and Development
Volume	18
Issue number	13
DOIs	https://doi.org/10.1101/gad.1194004
State	Published - Jul 1 2004

Keywords

BBS proteins
Bardet-Biedl syndrome
Basal body
Caenorhabditis elegans
Cilia and flagella
Intraflagellar transport

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Blacque, O. E., Reardon, M. J., Li, C., McCarthy, J., Mahjoub, M. R., Ansley, S. J., Badano, J. L., Mah, A. K., Beales, P. L., Davidson, W. S., Johnsen, R. C., Audeh, M., Plasterk, R. H. A., Baillie, D. L., Katsanis, N., Quarmby, L. M., Wicks, S. R., & Leroux, M. R. (2004). Loss of C. elegans BBS-7 and BBS-8 protein function results in cilia defects and compromised intraflagellar transport. Genes and Development, 18(13), 1630-1642. https://doi.org/10.1101/gad.1194004

@article{433380a0016a492bab25c298f58547fd,

title = "Loss of C. elegans BBS-7 and BBS-8 protein function results in cilia defects and compromised intraflagellar transport",

abstract = "Bardet-Biedl syndrome (BBS) is a genetically heterogeneous developmental disorder whose molecular basis is largely unknown. Here, we show that mutations in the Caenorhabditis elegans bbs-7 and bbs-8 genes cause structural and functional defects in cilia. C. elegans BBS proteins localize predominantly at the base of cilia, and like proteins involved in intraflagellar transport (IFT), a process necessary for cilia biogenesis and maintenance, move bidirectionally along the ciliary axoneme. Importantly, we demonstrate that BBS-7 and BBS-8 are required for the normal localization/motility of the IFT proteins OSM-5/Polaris and CHE-11, and to a notably lesser extent, CHE-2. We propose that BBS proteins play important, selective roles in the assembly and/or function of IFT particle components. Our findings also suggest that some of the cardinal and secondary symptoms of BBS, such as obesity, diabetes, cardiomyopathy, and learning defects may result from cilia dysfunction.",

keywords = "BBS proteins, Bardet-Biedl syndrome, Basal body, Caenorhabditis elegans, Cilia and flagella, Intraflagellar transport",

author = "Blacque, {Oliver E.} and Reardon, {Michael J.} and Chunmei Li and Jonathan McCarthy and Mahjoub, {Moe R.} and Ansley, {Stephen J.} and Badano, {Jose L.} and Mah, {Allan K.} and Beales, {Philip L.} and Davidson, {William S.} and Johnsen, {Robert C.} and Mark Audeh and Plasterk, {Ronald H.A.} and Baillie, {David L.} and Nicholas Katsanis and Quarmby, {Lynne M.} and Wicks, {Stephen R.} and Leroux, {Michel R.}",

year = "2004",

month = jul,

day = "1",

doi = "10.1101/gad.1194004",

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Blacque, OE, Reardon, MJ, Li, C, McCarthy, J, Mahjoub, MR, Ansley, SJ, Badano, JL, Mah, AK, Beales, PL, Davidson, WS, Johnsen, RC, Audeh, M, Plasterk, RHA, Baillie, DL, Katsanis, N, Quarmby, LM, Wicks, SR & Leroux, MR 2004, 'Loss of C. elegans BBS-7 and BBS-8 protein function results in cilia defects and compromised intraflagellar transport', Genes and Development, vol. 18, no. 13, pp. 1630-1642. https://doi.org/10.1101/gad.1194004

TY - JOUR

T1 - Loss of C. elegans BBS-7 and BBS-8 protein function results in cilia defects and compromised intraflagellar transport

AU - Blacque, Oliver E.

AU - Reardon, Michael J.

AU - Li, Chunmei

AU - McCarthy, Jonathan

AU - Mahjoub, Moe R.

AU - Ansley, Stephen J.

AU - Badano, Jose L.

AU - Mah, Allan K.

AU - Beales, Philip L.

AU - Davidson, William S.

AU - Johnsen, Robert C.

AU - Audeh, Mark

AU - Plasterk, Ronald H.A.

AU - Baillie, David L.

AU - Katsanis, Nicholas

AU - Quarmby, Lynne M.

AU - Wicks, Stephen R.

AU - Leroux, Michel R.

PY - 2004/7/1

Y1 - 2004/7/1

N2 - Bardet-Biedl syndrome (BBS) is a genetically heterogeneous developmental disorder whose molecular basis is largely unknown. Here, we show that mutations in the Caenorhabditis elegans bbs-7 and bbs-8 genes cause structural and functional defects in cilia. C. elegans BBS proteins localize predominantly at the base of cilia, and like proteins involved in intraflagellar transport (IFT), a process necessary for cilia biogenesis and maintenance, move bidirectionally along the ciliary axoneme. Importantly, we demonstrate that BBS-7 and BBS-8 are required for the normal localization/motility of the IFT proteins OSM-5/Polaris and CHE-11, and to a notably lesser extent, CHE-2. We propose that BBS proteins play important, selective roles in the assembly and/or function of IFT particle components. Our findings also suggest that some of the cardinal and secondary symptoms of BBS, such as obesity, diabetes, cardiomyopathy, and learning defects may result from cilia dysfunction.

AB - Bardet-Biedl syndrome (BBS) is a genetically heterogeneous developmental disorder whose molecular basis is largely unknown. Here, we show that mutations in the Caenorhabditis elegans bbs-7 and bbs-8 genes cause structural and functional defects in cilia. C. elegans BBS proteins localize predominantly at the base of cilia, and like proteins involved in intraflagellar transport (IFT), a process necessary for cilia biogenesis and maintenance, move bidirectionally along the ciliary axoneme. Importantly, we demonstrate that BBS-7 and BBS-8 are required for the normal localization/motility of the IFT proteins OSM-5/Polaris and CHE-11, and to a notably lesser extent, CHE-2. We propose that BBS proteins play important, selective roles in the assembly and/or function of IFT particle components. Our findings also suggest that some of the cardinal and secondary symptoms of BBS, such as obesity, diabetes, cardiomyopathy, and learning defects may result from cilia dysfunction.

KW - BBS proteins

KW - Bardet-Biedl syndrome

KW - Basal body

KW - Caenorhabditis elegans

KW - Cilia and flagella

KW - Intraflagellar transport

UR - http://www.scopus.com/inward/record.url?scp=3042738924&partnerID=8YFLogxK

U2 - 10.1101/gad.1194004

DO - 10.1101/gad.1194004

M3 - Article

C2 - 15231740

AN - SCOPUS:3042738924

SN - 0890-9369

VL - 18

SP - 1630

EP - 1642

JO - Genes and Development

JF - Genes and Development

IS - 13

ER -

Loss of C. elegans BBS-7 and BBS-8 protein function results in cilia defects and compromised intraflagellar transport

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Keywords

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