Cilia on the Brain: Primary Cilia and Their Roles in Brain Function

Abstract

The primary cilium was first discovered over 100 years ago but only relatively recently has it been widely regarded as an integral cellular organelle for brain development, maturation and function. Defects in primary cilia contribute to a set of human disorders, ciliopathies, which are multi‚Äźsystemic in pathology and often include abnormal CNS architecture and intellectual deficits. The intricate structure of the cilium and the molecules that localise to the axoneme all contribute to elegantly orchestrated signalling pathways that influence the whole cell. From their role in neural tube development, neuronal migration and differentiation, to their putative role in adult cognition, primary cilia are critical for diverse aspects of brain function. Yet our current understanding is still very limited: much remains to be discovered about primary cilia biology and ciliary function in the mammalian brain.

Key Concepts

  • Primary cilia are unusual cell organelles that look similar to antennae protruding from the cell.
  • Almost all brain cell types have primary cilia, which transduce signals from the milieu.
  • Ciliopathies in humans result from primary cilia defects and often include cognitive impairments and cortical malformations.
  • Primary cilia contribute to brain development and function.

Keywords: cilia; ciliopathy; IFT; axoneme; neurogenesis; neural patterning; memory; cognitive impairment

Figure 1. Primary cilia are found on most neuronal and glial cell types in the brain including but not limited to excitatory (blue) and inhibitory (orange) neurons, astrocytes (red), oligodendrocytes (purple) and radial glia (green). These organelles are associated with a number of important developmental and maintenance functions (listed in this figure) in the brain, but other functions not reviewed here can be found in the further reading list.
Figure 2. Primary cilia architecture is complex, yet elegant and conserved. The basal bodies of the cilium, composed of mother (MC) and daughter (DC) centrioles and made up of nine MT triplets, act to serve as not only the anchor of the axoneme to the cell but also the template from which the cilia axoneme is built. An amorphous protein matrix, termed the pericentriolar material (PCM), surrounds the basal bodies and contains proteins responsible for anchoring the MTs. The axoneme is comprised of nine MT doublets and a lack a central pair (9+0) of doublets found on most secondary, motile cilia (9+2). The majority of ciliary trafficking takes place upon this axoneme backbone through the help of several key molecules including the anterograde motors (kinesins), and the retrograde motors (dyneins). The BBSome is a protein complex made up of seven proteins including BBS1, BBS2, BBS4, BBS5, BBS7, BBS8 and BBS9. Additional BBS proteins have been identified and aid in the transport of other ciliary destined cargoes, such as intraflagellar transport (IFT) cargoes, G‐protein‐coupled receptors (GPCRs) and other receptor types (not shown here). IFT is a highly conserved mechanism the cilium uses for trafficking cargo. IFT proteins or particles are required for ciliogenesis, cilia maintenance and function. These proteins are categorised into two groups, the anterograde, or IFT‐B particles, and the IFT‐A, retrograde particles. Polarised vesicle trafficking is a mechanism by which ciliary proteins are transported through the subcellular architecture to the axoneme. From golgi‐derived vesicular budding, ciliary destined cargoes are trafficked to the basal body with the help of the exocyst (an octomeric protein complex), BBS particles and MTs. At the basal body, these cargoes are checked for a ciliary localisation sequence near the cilia pore complex and once approved, are allowed to pass through the transition zone (TZ) to the cilioplasmic space.
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Guadiana, Sarah M, and Grove, Elizabeth A(Feb 2015) Cilia on the Brain: Primary Cilia and Their Roles in Brain Function. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0025793]