Axonemal Lumen Dominates Cytosolic Protein Diffusion inside the Primary Cilium

Sci Rep. 2017 Nov 17;7(1):15793. doi: 10.1038/s41598-017-16103-z.

Abstract

Transport of membrane and cytosolic proteins in primary cilia is thought to depend on intraflagellar transport (IFT) and diffusion. However, the relative contribution and spatial routes of each transport mechanism are largely unknown. Although challenging to decipher, the details of these routes are essential for our understanding of protein transport in primary cilia, a critically affected process in many genetic diseases. By using a high-speed virtual 3D super-resolution microscopy, we have mapped the 3D spatial locations of transport routes for various cytosolic proteins in the 250-nm-wide shaft of live primary cilia with a spatiotemporal resolution of 2 ms and <16 nm. Our data reveal two spatially distinguishable transport routes for cytosolic proteins: an IFT-dependent path along the axoneme, and a passive-diffusion route in the axonemal lumen that escaped previous studies. While all cytosolic proteins tested primarily utilize the IFT path in the anterograde direction, differences are observed in the retrograde direction where IFT20 only utilizes IFT, and approximately half of KIF17 and one third of α-tubulin utilizes diffusion besides IFT.

MeSH terms

  • Animals
  • Axoneme / metabolism*
  • Carrier Proteins / metabolism
  • Cilia / metabolism*
  • Cytosol / metabolism*
  • Diffusion
  • Green Fluorescent Proteins / metabolism
  • Kinesins / metabolism
  • Mice
  • Microscopy
  • NIH 3T3 Cells
  • Probability
  • Protein Transport
  • Proteins / metabolism*
  • Tubulin / metabolism

Substances

  • Carrier Proteins
  • Ift20 protein, mouse
  • KIF17 protein, mouse
  • Proteins
  • Tubulin
  • Green Fluorescent Proteins
  • Kinesins