Neuronal and astrocytic primary cilia in the mature brain

Abstract

Primary cilia are tiny microtubule-based signaling devices that regulate a variety of physiological functions, including metabolism and cell division. Defects in primary cilia lead to a myriad of diseases in humans such as obesity and cancers. In the mature brain, both neurons and astrocytes contain a single primary cilium. Although neuronal primary cilia are not directly involved in synaptic communication, their pathophysiological impacts on obesity and mental disorders are well recognized. In contrast, research on astrocytic primary cilia lags far behind. Currently, little is known about their functions and molecular pathways in the mature brain. Unlike neurons, postnatal astrocytes retain the capacity of cell division and can become reactive and proliferate in response to various brain insults such as epilepsy, ischemia, traumatic brain injury, and neurodegenerative β-amyloid plaques. Since primary cilia derive from the mother centrioles, astrocyte proliferation must occur in coordination with the dismantling and ciliogenesis of astrocyte cilia. In this regard, the functions, signal pathways, and structural dynamics of neuronal and astrocytic primary cilia are fundamentally different. Here we discuss and compare the current understanding of neuronal and astrocytic primary cilia.

Diverged morphology changes of astrocytic and neuronal primary cilia under reactive insults

“…The mother centriole forms the base of the primary cilium, and comprises the centrosome with the daughter centriole during interphase [1,40]. It has been widely thought that Centrin2 is a marker protein of the centrosome, and the Centrin2-GFP of Arl mice has been used to mark the centrosome in multiple developmental studies [33,[41][42][43][44].…”

“…AC3 is mostly enriched in neuronal primary cilia, while Arl13b is widely expressed in astrocytic primary cilia in the adult mouse brain [1,17]. To date, it is not clear how spontaneous seizures affect Arl13b-positive astrocytic cilia and AC3-positive neuronal cilia.…”

“…Primary cilia are microtubule-based sensory organelles present in most mammalian cells, including neurons and astrocytes in the brain [1,2]. The microenvironment of primary cilia is distinct from actin-based microdomains such as microvilli and synapses.…”

“…Although neurons and astrocytes originate from the same precursors in early neurodevelopment, their primary cilia demonstrate a dichotomy in the mature brain [1]: their signaling pathways and molecular components, marker proteins [1,17], ciliary nanoscale structure (communicated by Carolyn Ott from Janelia Research Campus in 2019), and functionality, as well as disease associations, are markedly diverged. In the adult brain, neuronal and astrocytic primary cilia are generally marked by type 3 adenylyl cyclase (AC3) [18] and ADP-ribosylation factorlike protein 13b (Arl13b), respectively [1]. AC3 represents a key enzyme mediating cAMP signaling in neuronal primary cilia throughout the mature brain [4].…”

TTBK2 and primary cilia are essential for the connectivity and survival of cerebellar Purkinje neurons

“…During development, ciliary signals drive the proliferation and patterning of neural progenitor populations (Guemez-Gamboa et al, 2014). Cilia then persist on post-mitotic neurons during development and through adulthood (Sterpka and Chen, 2018). However, we have only an incomplete understanding of the roles for primary cilia on differentiated, post-mitotic neurons, particularly within the adult brain.…”