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Autores principales: Hong, Juyeon, Lee, Chanjae, Madhu, Gopika, Papoulas, Ophelia, Atayeter, Ece, Hoogerbrugge, Gabriel, Pan, Jiehong, Takagishi, Maki, Manzi, Nadia I, Dickinson, Daniel J, Horani, Amjad, Brody, Steven L, Marcotte, Edward M, Prakash, Vivek N, Park, Tae Joo, Wallingford, John B
Formato: Artículo científico
Lenguaje:en
Publicado: Nature communications 2025
Materias:
Acceso en línea:https://pubmed.ncbi.nlm.nih.gov/41423487/
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author Hong, Juyeon
Lee, Chanjae
Madhu, Gopika
Papoulas, Ophelia
Atayeter, Ece
Hoogerbrugge, Gabriel
Pan, Jiehong
Takagishi, Maki
Manzi, Nadia I
Dickinson, Daniel J
Horani, Amjad
Brody, Steven L
Marcotte, Edward M
Prakash, Vivek N
Park, Tae Joo
Wallingford, John B
author_facet Hong, Juyeon
Lee, Chanjae
Madhu, Gopika
Papoulas, Ophelia
Atayeter, Ece
Hoogerbrugge, Gabriel
Pan, Jiehong
Takagishi, Maki
Manzi, Nadia I
Dickinson, Daniel J
Horani, Amjad
Brody, Steven L
Marcotte, Edward M
Prakash, Vivek N
Park, Tae Joo
Wallingford, John B
Hong, Juyeon
Lee, Chanjae
Madhu, Gopika
Papoulas, Ophelia
Atayeter, Ece
Hoogerbrugge, Gabriel
Pan, Jiehong
Takagishi, Maki
Manzi, Nadia I
Dickinson, Daniel J
Horani, Amjad
Brody, Steven L
Marcotte, Edward M
Prakash, Vivek N
Park, Tae Joo
Wallingford, John B
collection PubMed - marine biology
contents A protein complex in the extreme distal tip of vertebrate motile cilia controls their organization, length, and function. Hong, Juyeon Lee, Chanjae Madhu, Gopika Papoulas, Ophelia Atayeter, Ece Hoogerbrugge, Gabriel Pan, Jiehong Takagishi, Maki Manzi, Nadia I Dickinson, Daniel J Horani, Amjad Brody, Steven L Marcotte, Edward M Prakash, Vivek N Park, Tae Joo Wallingford, John B Cilia Animals Mice Humans Microtubules Xenopus laevis Multiprotein Complexes The beating of cilia on multi-ciliated cells (MCCs) is essential for normal development and homeostasis in animals. But while the structure and function of basal bodies and axonemes have received significant attention recently, the distal tips of MCC cilia remain relatively poorly defined. Here, we characterize the molecular organization of the distal tip of vertebrate MCC cilia, characterizing two distinct domains occupied by distinct protein constituents. Using frog, mouse, and human MCCs, we find that two largely uncharacterized proteins, Ccdc78 and Ccdc33, occupy a previously undefined region at the extreme distal tip, and these are required for the normal organization of all other known tip proteins. Ccdc78 and Ccdc33 each display robust microtubule-bundling activity both in vivo and in vitro, yet each is independently required for normal length regulation of MCC cilia. Moreover, loss of each protein elicits a distinct pattern of defective cilia beating and resultant fluid flow. Thus, two previously undefined proteins form a key module essential for organizing and stabilizing the distal tip of motile cilia in vertebrate MCCs. We propose that these ill-defined proteins represent potential disease loci for motile ciliopathies.
format Artículo científico
id pubmed_41423487
institution PubMed
language en
publishDate 2025
publisher Nature communications
record_format pubmed
spellingShingle A protein complex in the extreme distal tip of vertebrate motile cilia controls their organization, length, and function.
Hong, Juyeon
Lee, Chanjae
Madhu, Gopika
Papoulas, Ophelia
Atayeter, Ece
Hoogerbrugge, Gabriel
Pan, Jiehong
Takagishi, Maki
Manzi, Nadia I
Dickinson, Daniel J
Horani, Amjad
Brody, Steven L
Marcotte, Edward M
Prakash, Vivek N
Park, Tae Joo
Wallingford, John B
Cilia
Animals
Mice
Humans
Microtubules
Xenopus laevis
Multiprotein Complexes
A protein complex in the extreme distal tip of vertebrate motile cilia controls their organization, length, and function. Hong, Juyeon Lee, Chanjae Madhu, Gopika Papoulas, Ophelia Atayeter, Ece Hoogerbrugge, Gabriel Pan, Jiehong Takagishi, Maki Manzi, Nadia I Dickinson, Daniel J Horani, Amjad Brody, Steven L Marcotte, Edward M Prakash, Vivek N Park, Tae Joo Wallingford, John B Cilia Animals Mice Humans Microtubules Xenopus laevis Multiprotein Complexes The beating of cilia on multi-ciliated cells (MCCs) is essential for normal development and homeostasis in animals. But while the structure and function of basal bodies and axonemes have received significant attention recently, the distal tips of MCC cilia remain relatively poorly defined. Here, we characterize the molecular organization of the distal tip of vertebrate MCC cilia, characterizing two distinct domains occupied by distinct protein constituents. Using frog, mouse, and human MCCs, we find that two largely uncharacterized proteins, Ccdc78 and Ccdc33, occupy a previously undefined region at the extreme distal tip, and these are required for the normal organization of all other known tip proteins. Ccdc78 and Ccdc33 each display robust microtubule-bundling activity both in vivo and in vitro, yet each is independently required for normal length regulation of MCC cilia. Moreover, loss of each protein elicits a distinct pattern of defective cilia beating and resultant fluid flow. Thus, two previously undefined proteins form a key module essential for organizing and stabilizing the distal tip of motile cilia in vertebrate MCCs. We propose that these ill-defined proteins represent potential disease loci for motile ciliopathies.
title A protein complex in the extreme distal tip of vertebrate motile cilia controls their organization, length, and function.
topic Cilia
Animals
Mice
Humans
Microtubules
Xenopus laevis
Multiprotein Complexes
url https://pubmed.ncbi.nlm.nih.gov/41423487/