Olfactory cilia: linking sensory cilia function and human disease

Abstract

The olfactory system gives us an awareness of our immediate environment by allowing us to detect airborne stimuli. The components necessary for detection of these odorants are compartmentalized in the cilia of olfactory sensory neurons. Cilia are microtubule-based organelles, which can be found projecting from the surface of almost any mammalian cell, and are critical for proper olfactory function. Mislocalization of ciliary proteins and/or the loss of cilia cause impaired olfactory function, which is now recognized as a clinical manifestation of a broad class of human diseases, termed ciliopathies. Future work investigating the mechanisms of olfactory cilia function will provide us important new information regarding the pathogenesis of human sensory perception diseases.

Figure 1

Anatomy of the OE and OSN. (A) Side view of a scanning electron micrograph at 1030× magnification from mouse OE. Mouse OE was dissected, fixed in glutaraldehyde, and processed for scanning electron microscopy as previously described (McEwen et al. 2007). Scanning electron micrographs were captured using an Amray 1910FE field emission scanning electron microscope at 5 kV. Images were recorded digitally with Semicaps software. Layers of the OE are labeled in white. Cilia layer marked by bracket. Sus. Cells = sustentacular cells. Scale bar represents 10 μm. (Image generously provided by Wanda Layman and Dr Donna Martin, Department of Human Genetics, University of Michigan). (B) Diagram of a single OSN. Boxed region of interest at base of cilium shown at higher magnification in panel C. (C) Diagram of olfactory cilium and associated organelles. Cross sections of axonemal configuration from distal segment (top), proximal segment (middle), and basal body (bottom) shown on the right. Solidi (//) mark transition from proximal to distal segments. MTOC = Microtubule Organizing Center. +s indicate plus ends of microtubules. (D) Diagram of the ciliary and basal body components involved in olfactory ciliary transport. Anterograde motors move cargo to the distal tip of the cilium. Heterotrimeric kinesin-II is composed of KIF3a, KIF3b, and KAP3, whereas KIF17 comprises a homodimer. The retrograde motor, cytoplasmic dynein 1b moves cargo back out of the cilium. IFT complexes are shown as gray circles. BBS proteins, CEP290, and PACS-1 are discussed in detail in the Selectivity of Ciliary Protein Entry section.

Figure 2

Localization of Olfactory Signaling Proteins to Cilia. Immunocytochemistry for olfactory signaling proteins was performed on 14-mm-thick sections of frozen mouse OE as described previously (McEwen et al. 2007). Acetylated α tubulin is a marker for the cilia layer. The odorant receptor mOR28 (top middle, antibody courtesy of Dr Richard Axel) is localized throughout the OSN including the cilia, which can be more easily visualized in an en face section (top right). The olfactory G protein Gα_olf (bottom left), adenylyl cyclase III (bottom middle), and CNG channel CNGA2 subunit (bottom right) are all enriched in the cilia layer. NC = nasal cavity, OE = olfactory epithelium. Scale bars represent 10 μm for all images except en face mOR28 (bar represents 5 μm).

Figure 3

Steps of Ciliogenesis in the OSN. (A) In a developing OSN (at approximately E10–E11) centrioles are duplicated en masse from the mother/daughter centrioles in the cell body before migrating along the developing dendrite toward the eventual dendritic knob (B). (C) In the dendritic knob (at approximately E12–E14), centrioles are converted to basal bodies and anchored to the plasma membrane, and ciliogenesis begins as the ciliary axonemes extend from the basal body and elongate the cilia into the mucous layer where odorant transduction occurs (D) Interestingly, 1 single primary cilium of approximately 1 μm in length forms before the appearance of the remaining cilia.