NPHP4 controls ciliary trafficking of membrane proteins and large soluble proteins at the transition zone
Department of Cell and Developmental Biology; Biomedical Imaging Group; Program in Molecular Medicine
Cell and Developmental Biology | Cell Biology
The protein nephrocystin-4 (NPHP4) is widespread in ciliated organisms, and defects in NPHP4 cause nephronophthisis and blindness in humans. To learn more about the function of NPHP4, we have studied it in Chlamydomonas reinhardtii. NPHP4 is stably incorporated into the distal part of the flagellar transition zone, close to the membrane and distal to CEP290, another transition zone protein. Therefore, these two proteins, which are incorporated into the transition zone independently of each other, define different domains of the transition zone. An nphp4-null mutant forms flagella with nearly normal length, ultrastructure and intraflagellar transport. When fractions from isolated wild-type and nphp4 flagella were compared, few differences were observed between the axonemes, but the amounts of certain membrane proteins were greatly reduced in the mutant flagella, and cellular housekeeping proteins > 50 kDa were no longer excluded from mutant flagella. Therefore, NPHP4 functions at the transition zone as an essential part of a barrier that regulates both membrane and soluble protein composition of flagella. The phenotypic consequences of NPHP4 mutations in humans likely follow from protein mislocalization due to defects in the transition zone barrier.
CEP290, Chlamydomonas, Cilia, Flagella, Nephrocystin-4, Transition zone
DOI of Published Version
J Cell Sci. 2014 Nov 1;127(21):4714-27. doi: 10.1242/jcs.155275. Link to article on publisher's site.
Journal of cell science
Awata, Junya; Takada, Saeko; Standley, Clive; Lechtreck, Karl-Ferdinand; Bellve, Karl D.; Pazour, Gregory J.; Fogarty, Kevin E.; and Witman, George B., "NPHP4 controls ciliary trafficking of membrane proteins and large soluble proteins at the transition zone" (2014). Cell and Developmental Biology Publications. 144.