NUP98 Sets the Size-Exclusion Diffusion Limit through the Ciliary Base.

NUP98 Sets the Size-Exclusion Diffusion Limit through the Ciliary Base.
Curr Biol. 2018 Apr 26;:
Authors: Endicott SJ, Brueckner M
Abstract
The primary cilium maintains a well-regulated complement of soluble and membrane proteins, allowing it to mediate a variety of signaling pathways that are essential for development and tissue homeostasis [1-3]. Entry into the cilium is regulated at the base, where a complex containing nucleoporins, referred to as the "ciliary pore complex" (CPC), has been proposed to set a size-exclusion limit for soluble molecule diffusion into the cilium [4-6]. Here, using a fluorescence-based diffusion trap system, we demonstrate that NUP98, a component of the phenylalanine-glycine (FG) hydrogel permeability barrier at the nuclear pore complex [7, 8], limits the diffusion of soluble molecules >70 kDa into the cilium in cultured mammalian cells. Small interfering RNA (siRNA)-mediated knockdown of NUP98 increases the rate of diffusion of molecules >100 kDa into the cilium. The tubulin heterodimer, the building block of the axoneme [9, 10], is approximately 100 kDa in size. After knockdown of NUP98, cilia become shorter, and their length is more sensitive to changes in cytoplasmic soluble tubulin levels. These data indicate a novel function of the ciliary pore complex, limiting diffusion of soluble tubulin between the ciliary matrix and the cytosol, allowing the cilium to regulate its length independentl...

Source: Current Biology - April 26, 2018 Category: Biology Authors: Endicott SJ, Brueckner M Tags: Curr Biol Source Type: research