Pericentrin forms a complex with intraflagellar transport proteins and polycystin-2 and is required for primary cilia assembly

نویسندگان

  • Agata Jurczyk
  • Adam Gromley
  • Sambra Redick
  • Jovenal San Agustin
  • George Witman
  • Gregory J. Pazour
  • Dorien J.M. Peters
  • Stephen Doxsey
چکیده

Primary cilia are nonmotile microtubule structures that assemble from basal bodies by a process called intraflagellar transport (IFT) and are associated with several human diseases. Here, we show that the centrosome protein pericentrin (Pcnt) colocalizes with IFT proteins to the base of primary and motile cilia. Immunogold electron microscopy demonstrates that Pcnt is on or near basal bodies at the base of cilia. Pcnt depletion by RNA interference disrupts basal body localization of IFT proteins and the cation channel polycystin-2 (PC2), and inhibits primary cilia assembly in human epithelial cells. Conversely, silencing of IFT20 mislocalizes Pcnt from basal bodies and inhibits primary cilia assembly. Pcnt is found in spermatocyte IFT fractions, and IFT proteins are found in isolated centrosome fractions. Pcnt antibodies coimmunoprecipitate IFT proteins and PC2 from several cell lines and tissues. We conclude that Pcnt, IFTs, and PC2 form a complex in vertebrate cells that is required for assembly of primary cilia and possibly motile cilia and flagella.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

The intraflagellar transport protein IFT20 is associated with the Golgi complex and is required for cilia assembly.

Eukaryotic cilia are assembled via intraflagellar transport (IFT) in which large protein particles are motored along ciliary microtubules. The IFT particles are composed of at least 17 polypeptides that are thought to contain binding sites for various cargos that need to be transported from their site of synthesis in the cell body to the site of assembly in the cilium. We show here that the IFT...

متن کامل

The Intraflagellar Transport Protein IFT20 Is Associated with the Golgi Complex and Is Required for Cilia Assembly□V

Eukaryotic cilia are assembled via intraflagellar transport (IFT) in which large protein particles are motored along ciliary microtubules. The IFT particles are composed of at least 17 polypeptides that are thought to contain binding sites for various cargos that need to be transported from their site of synthesis in the cell body to the site of assembly in the cilium. We show here that the IFT...

متن کامل

Polycystin-2 localizes to kidney cilia and the ciliary level is elevated in orpk mice with polycystic kidney disease

Defects in the PKD1 and PKD2 genes cause autosomal dominant polycystic kidney disease (PKD) in ~1 in 1000 adults worldwide. These genes encode polycystin-1 and polycystin-2, which are membrane proteins thought to be involved in a calcium signal transduction cascade that controls epithelial proliferation and differentiation. Individuals with mutations in these genes develop cysts in the ducts an...

متن کامل

Pericentrin pivotal in primary cilia

Pericentrin pivotal in primary cilia he centrosome protein pericentrin acts as an anchor for primary cilia formation in human cells, according to a report by Jurczyk et al. (page 637). The finding further unites the centrosome and primary cilia, both of which are based around centri-oles, and both of which use pericentrin as an anchor for other proteins. The authors show that pericentrin is loc...

متن کامل

Intraflagellar Transport Is Required for the Vectorial Movement of TRPV Channels in the Ciliary Membrane

The membranes of all eukaryotic motile (9 + 2) and immotile primary (9 + 0) cilia harbor channels and receptors involved in sensory transduction (reviewed by). These membrane proteins are transported from the cytoplasm onto the ciliary membrane by vesicles targeted for exocytosis at a point adjacent to the ciliary basal body. Here, we use time-lapse fluorescence microscopy to demonstrate that s...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • The Journal of Cell Biology

دوره 166  شماره 

صفحات  -

تاریخ انتشار 2004