Neuronal Primary Cilia: An Underappreciated Signaling and Sensory Organelle in the Brain

Green, Jill A.; Mykytyn, Kirk

doi:10.1038/npp.2013.203

Cited by 52 publications

(44 citation statements)

References 6 publications

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“…While studies of Kif3a, Lkb1, and Rfx3 knockout mice have all invoked a role for cilia in pancreatic development (i.e., ductal and endocrine cell specification) [87,[89][90][91], little is known about their involvement in cell-cell signaling processes within the islet. Given the role of cilia in signal transmission in in other tissues [92], and potentially in exosome-mediated intercellular communications [93], we believe this warrants further investigation. Paracrine signaling Intercellular communication may also be possible via the production and secretion of messengers which act on neighboring cells [20,21,28].…”

Section: Primary Ciliamentioning

confidence: 94%

Beta cell connectivity in pancreatic islets: a type 2 diabetes target?

Rutter

Hodson

2014

Cell. Mol. Life Sci.

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Beta cell connectivity describes the phenomenon whereby the islet context improves insulin secretion by providing a three-dimensional platform for intercellular signaling processes. Thus, the precise flow of information through homotypically interconnected beta cells leads to the large-scale organization of hormone release activities, influencing cell responses to glucose and other secretagogues. Although a phenomenon whose importance has arguably been underappreciated in islet biology until recently, a growing number of studies suggest that such cell-cell communication is a fundamental property of this micro-organ. Hence, connectivity may plausibly be targeted by both environmental and genetic factors in type 2 diabetes mellitus (T2DM) to perturb normal beta cell function and insulin release. Here, we review the mechanisms that contribute to beta cell connectivity, discuss how these may fail during T2DM, and examine approaches to restore insulin secretion by boosting cell communication.

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Section: Primary Ciliamentioning

confidence: 94%

Beta cell connectivity in pancreatic islets: a type 2 diabetes target?

Rutter

Hodson

2014

Cell. Mol. Life Sci.

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“…For example, conditional ablation of cilia has been shown to result in disrupted dendritic arborization and the establishment of neuronal networks [118]. In addition, cilia are being shown to participate in diverse aspects of neuronal biology such as maintenance of progenitor pools, neurogenesis and neuronal migration, findings that will promote a better understanding of the cellular basis of the different CNS defects that characterize BBS and other ciliopathies (for thorough reviews on the role of cilia in the CNS see [119,120]). …”

Section: Central Nervous Systemmentioning

confidence: 99%

Bardet–Biedl syndrome: Is it only cilia dysfunction?

et al. 2015

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a b s t r a c tBardet-Biedl syndrome (BBS) is a genetically heterogeneous, pleiotropic disorder, characterized by both congenital and late onset defects. From the analysis of the mutational burden in patients to the functional characterization of the BBS proteins, this syndrome has become a model for both understanding oligogenic patterns of inheritance and the biology of a particular cellular organelle: the primary cilium. Here we briefly review the genetics of BBS to then focus on the function of the BBS proteins, not only in the context of the cilium but also highlighting potential extra-ciliary roles that could be relevant to the etiology of the disorder. Finally, we provide an overview of how the study of this rare syndrome has contributed to the understanding of cilia biology and how this knowledge has informed on the cellular basis of different clinical manifestations that characterize BBS and the ciliopathies.

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“…Also at brain level, it is possible to distinguish motile cilia that are found only in some cells, such as those lining the brain ventricles (Guirao et al, 2010;Louvi and Grove, 2011) from the non-motile primary cilia, which are solitary appendages present in most neurons and astrocytes. Non-motile primary cilia are capable of detecting various extracellular signals and transmit them to the cell cytoplasm (Green and Mykytyn, 2014;Kasahara et al, 2014 The present proposal suggests that some of the main biochemical mechanisms involved in 'cell sentience' are affected by proteins exploring their energy landscape under the action of the physicochemical conditions of the environments in which they are embedded. On the other hand, the phenomenon of cell sentience is causally linked not only to the spontaneous activity of CCNs but also to the intercellular communication processes that allow integrative brain mechanisms.…”

Section: Introductionmentioning

confidence: 73%

“…In fact, a particular cell membrane specialization, namely, the primary cilium (Lee and Gleeson, 2011;Louvi and Grove, 2011;Green and Mykytyn, 2014), can play a special role in the cellular response to the extracellular environment signals, as it works like an 'intelligent nano-antenna' (Singla and Reiter, 2006). Thus, such a cellular organelle is capable of recognizing different physicochemical stimuli present in the extracellular environment and of transducing them into specific intracellular signals capable of modulating peculiar cellular functions; in particular, it can play a basic role in neural signaling (Phua et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

“…As discussed above and previously proposed by our group (Agnati et al, 1982(Agnati et al, , 1983(Agnati et al, , 2010bFuxe and Agnati, 1985;Guidolin et al, 2015), GPCR-GPCR receptor-receptor interactions can lead to changes in ligand binding properties, receptor desensitization, and internalization or can even lead to the activation of completely new intracellular decoding molecular pathways. Thus, it can be surmised that primary cilia possess peculiar horizontal molecular networks (HMNs), and the chemical and physical properties of these appendages suggest that cilia represent a specialized cell organelle capable of integrative actions of extracellular signals and of complex crosstalks with the cell cytoplasm (Nachury, 2014;Green and Mykytyn, 2014).…”

Section: Introductionmentioning

confidence: 99%

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The multi-facet aspects of cell sentience and their relevance for the integrative brain actions: role of membrane protein energy landscape

Agnati¹,

Marcoli

Maura

et al. 2016

Reviews in the Neurosciences

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AbstractSeveral ion channels can be randomly and spontaneously in an open state, allowing the exchange of ion fluxes between extracellular and intracellular environments. We propose that the random changes in the state of ion channels could be also due to proteins exploring their energy landscapes. Indeed, proteins can modify their steric conformation under the effects of the physicochemical parameters of the environments with which they are in contact, namely, the extracellular, intramembrane and intracellular environments. In particular, it is proposed that the random walk of proteins in their energy landscape is towards attractors that can favor the open or close condition of the ion channels and/or intrinsic activity of G-protein-coupled receptors. The main aspect of the present proposal is that some relevant physicochemical parameters of the environments (e.g. molecular composition, temperature, electrical fields) with which some signaling-involved plasma membrane proteins are in contact alter their conformations. In turn, these changes can modify their information handling via a modulatory action on their random walk towards suitable attractors of their energy landscape. Thus, spontaneous and/or signal-triggered electrical activities of neurons occur that can have emergent properties capable of influencing the integrative actions of brain networks. Against this background, Cook’s hypothesis on ‘cell sentience’ is developed by proposing that physicochemical parameters of the environments with which the plasma-membrane proteins of complex cellular networks are in contact fulfill a fundamental role in their spontaneous and/or signal-triggered activity. Furthermore, it is proposed that a specialized organelle, the primary cilium, which is present in most cells (also neurons and astrocytes), could be of peculiar importance to pick up chemical signals such as ions and transmitters and to detect physical signals such as pressure waves, thermal gradients, and local field potentials.

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Neuronal Primary Cilia: An Underappreciated Signaling and Sensory Organelle in the Brain

Cited by 52 publications

References 6 publications

Beta cell connectivity in pancreatic islets: a type 2 diabetes target?

Beta cell connectivity in pancreatic islets: a type 2 diabetes target?

Bardet–Biedl syndrome: Is it only cilia dysfunction?

The multi-facet aspects of cell sentience and their relevance for the integrative brain actions: role of membrane protein energy landscape

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