Loss of Ift74 Leads to Slow Photoreceptor Degeneration and Ciliogenesis Defects in Zebrafish.

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, [2000-

Carrier Proteins/*metabolism ; Cilia/*pathology ; Photoreceptor Cells, Vertebrate/*pathology ; Retinal Degeneration/*pathology ; Zebrafish Proteins/*deficiency; Animals ; Cilia/metabolism ; Photoreceptor Cells, Vertebrate/metabolism ; Protein Transport ; Retinal Degeneration/metabolism ; Zebrafish

Cilia are microtubule-based structures projecting from the cell surface that perform diverse biological functions. Ciliary defects can cause a wide range of genetic disorders known collectively as ciliopathies. Intraflagellar transport (IFT) proteins are essential for the assembly and maintenance of cilia by transporting proteins along the axoneme. Here, we report a lack of Ift74, a core IFT-B protein, leading to ciliogenesis defects in multiple organs during early zebrafish development. Unlike rapid photoreceptor cell death in other ift-b mutants, the photoreceptors of ift74 mutants exhibited a slow degeneration process. Further experiments demonstrated that the connecting cilia of ift74 mutants were initially formed but failed to maintain, which resulted in slow opsin transport efficiency and eventually led to photoreceptor cell death. We also showed that the large amount of maternal ift74 transcripts deposited in zebrafish eggs account for the main reason of slow photoreceptor degeneration in the mutants. Together, our data suggested Ift74 is critical for ciliogenesis and that Ift proteins play variable roles in different types of cilia during early zebrafish development. To our knowledge, this is the first study to show ift-b mutant that displays slow photoreceptor degeneration in zebrafish.

J Cell Sci. 2008 Jun 1;121(11):1907-15. (PMID: 18492793)
Sci China Life Sci. 2021 Aug;64(8):1236-1280. (PMID: 33893979)
Proc Natl Acad Sci U S A. 2012 Feb 14;109(7):2388-93. (PMID: 22308397)
J Biol Chem. 2017 Oct 20;292(42):17375-17386. (PMID: 28855254)
Front Cell Dev Biol. 2021 Feb 04;9:636737. (PMID: 33614665)
Dev Cell. 2014 Nov 10;31(3):279-290. (PMID: 25446516)
Front Cell Dev Biol. 2021 May 19;9:661350. (PMID: 34095126)
Science. 2013 Aug 30;341(6149):1009-12. (PMID: 23990561)
Prog Retin Eye Res. 2016 Nov;55:52-81. (PMID: 27260426)
J Biol Chem. 2016 Nov 18;291(47):24465-24474. (PMID: 27681595)
Neuron. 2004 Jun 10;42(5):703-16. (PMID: 15182712)
Trends Biochem Sci. 2015 Dec;40(12):765-778. (PMID: 26498262)
Development. 2009 Sep;136(18):3089-98. (PMID: 19700616)
Nat Genet. 2018 Dec;50(12):1666-1673. (PMID: 30420648)
Mol Biol Cell. 2010 Dec;21(23):4076-88. (PMID: 20926680)
Dev Cell. 2014 Nov 10;31(3):265-278. (PMID: 25443296)
Hum Genet. 2021 Jul;140(7):1031-1043. (PMID: 33689014)
J Genet Genomics. 2016 Mar 20;43(3):107-20. (PMID: 27020031)
Eur J Hum Genet. 2020 Jul;28(7):943-946. (PMID: 32144365)
N Engl J Med. 2011 Apr 21;364(16):1533-43. (PMID: 21506742)
Genet Med. 2021 Jun;23(6):1041-1049. (PMID: 33531668)
FASEB J. 2015 Dec;29(12):4866-80. (PMID: 26229057)
J Cell Biol. 2002 Apr 1;157(1):103-13. (PMID: 11916979)
Development. 1990 Jul;109(3):567-76. (PMID: 2401210)
Vision Res. 2009 Feb;49(4):479-89. (PMID: 19136023)
Nat Cell Biol. 2008 Apr;10(4):437-44. (PMID: 18364699)
FEBS Lett. 2003 Oct 9;553(1-2):90-4. (PMID: 14550552)
Am J Hum Genet. 2016 Aug 4;99(2):318-36. (PMID: 27486776)
EMBO J. 2011 May 20;30(13):2532-44. (PMID: 21602787)
Cell. 2000 Jul 21;102(2):175-87. (PMID: 10943838)
Curr Opin Cell Biol. 2016 Apr;39:84-92. (PMID: 26926036)
J Med Genet. 2015 Aug;52(8):514-22. (PMID: 26092869)
Curr Biol. 2018 Apr 23;28(8):R421-R434. (PMID: 29689227)
Front Pediatr. 2018 Feb 13;6:23. (PMID: 29487844)
Cell Res. 2013 Apr;23(4):465-72. (PMID: 23528705)

202064009 Fundamental Research Funds for the Central Universities; MS2019NO02 Qingdao National Laboratory for Marine Science and Technology; 201941004 Fundamental Research Funds for the Central Universities; 201961016 Fundamental Research Funds for the Central Universities

Keywords: cilia; ift74; opsin transport; photoreceptor degeneration; zebrafish

0 (Carrier Proteins)
0 (Zebrafish Proteins)

Date Created: 20210910 Date Completed: 20211018 Latest Revision: 20211018

20221213

PMC8431285

10.3390/ijms22179329

34502236