Arf4 is required for Mammalian development but dispensable for ciliary assembly.

Citation data:

PLoS genetics, ISSN: 1553-7404, Vol: 10, Issue: 2, Page: e1004170

Publication Year:
2014
Usage 6047
Full Text Views 5766
Abstract Views 130
Downloads 104
Views 47
Captures 30
Readers 30
Social Media 1
Tweets 1
Citations 13
Citation Indexes 13
Repository URL:
https://escholarship.umassmed.edu/gsbs_sp/1854
PMID:
24586199
DOI:
10.1371/journal.pgen.1004170; 10.1371/journal.pgen.1004170.g004; 10.1371/journal.pgen.1004170.g005; 10.1371/journal.pgen.1004170.g002; 10.1371/journal.pgen.1004170.g006; 10.1371/journal.pgen.1004170.g001; 10.1371/journal.pgen.1004170.g003; 10.1371/journal.pgen.1004170.t001
PMCID:
PMC3930517; 3930517
Author(s):
John A. Follit; Jovenal T. San Agustin; Julie A. Jonassen; Tingting Huang; Jaime A. Rivera-Perez; Kimberly D. Tremblay; Gregory J. Pazour; Susan K. Dutcher
Publisher(s):
Public Library of Science (PLoS); Figshare
Tags:
Agricultural and Biological Sciences; Biochemistry, Genetics and Molecular Biology; Medicine; Biological Sciences; developmental biology; embryology; genetics; Gene function; interacts; ciliary; targeting; mutant; embryos; defects; visceral; concentrated; endoderm; mice; embryonic; knockdown; delays; cts; trafficking; nodal; mammalian; dispensable; gene function; Cell Biology; Developmental Biology; Molecular Genetics
Most Recent Tweet View All Tweets
article media
article description
The primary cilium is a sensory organelle, defects in which cause a wide range of human diseases including retinal degeneration, polycystic kidney disease and birth defects. The sensory functions of cilia require specific receptors to be targeted to the ciliary subdomain of the plasma membrane. Arf4 has been proposed to sort cargo destined for the cilium at the Golgi complex and deemed a key regulator of ciliary protein trafficking. In this work, we show that Arf4 binds to the ciliary targeting sequence (CTS) of fibrocystin. Knockdown of Arf4 indicates that it is not absolutely required for trafficking of the fibrocystin CTS to cilia as steady-state CTS levels are unaffected. However, we did observe a delay in delivery of newly synthesized CTS from the Golgi complex to the cilium when Arf4 was reduced. Arf4 mutant mice are embryonic lethal and die at mid-gestation shortly after node formation. Nodal cilia appeared normal and functioned properly to break left-right symmetry in Arf4 mutant embryos. At this stage of development Arf4 expression is highest in the visceral endoderm but we did not detect cilia on these cells. In the visceral endoderm, the lack of Arf4 caused defects in cell structure and apical protein localization. This work suggests that while Arf4 is not required for ciliary assembly, it is important for the efficient transport of fibrocystin to cilia, and also plays critical roles in non-ciliary processes.