Primary cilia and coordination of receptor tyrosine kinase (RTK) signalling

Abstract

Primary cilia are microtubule-based sensory organelles that coordinate signalling pathways in cell-cycle control, migration, differentiation and other cellular processes critical during development and for tissue homeostasis. Accordingly, defects in assembly or function of primary cilia lead to a plethora of developmental disorders and pathological conditions now known as ciliopathies. In this review, we summarize the current status of the role of primary cilia in coordinating receptor tyrosine kinase (RTK) signalling pathways. Further, we present potential mechanisms of signalling crosstalk and networking in the primary cilium and discuss how defects in ciliary RTK signalling are linked to human diseases and disorders.

Cilia and coordination of signaling networks during heart development

“…By these means, primary cilia control cellular processes during development and in the adult organism. 20,[27][28][29][30][31][32][33][34][35][36] In addition, specialized non-motile sensory cilia are present on neurons in the olfactory epithelium of the nasal Table 1. Common types of congenital heart defects Congenital heart defect Abbreviation Characteristics…”

PDGFRα signaling in the primary cilium regulates NHE1-dependent fibroblast migration via coordinated differential activity of MEK1/2-ERK1/2-p90RSK and AKT signaling pathways

“…The primary cilium found on most mammalian and human cells is a signaling center for normal developmental and physiological processes in the body (Christensen et al, 2012;Goetz and Anderson, 2010;Satir et al, 2010;Wallingford and Mitchell, 2011). When ciliogenesis is abnormal or the signal transduction pathway does not function properly, often because specific receptors are not properly localized to the ciliary membrane, the result is a series of pathologies, now called ciliopathies, such as cystic kidney disease or a failure of tissue repair as in wound healing or cardiac remodeling (Christensen et al, 2008;Hildebrandt et al, 2011;Waters and Beales, 2011).…”

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

“…Thus, according to our hypothesis, the activity of some key CCNs is goal-oriented, owing to the preferential conformations of some plasma membrane proteins that favor peculiar integrative actions at the meso-scale and macro-scale levels. Furthermore, the preferential detection and decoding of peculiar extracellular signals at primary cilium level can have marked effects not only on cell development and homeostasis but also on the information handling by the cell (Christensen et al, 2012;Louvi and Grove, 2011;Agnati et al, 2014; see also 'The multi facet aspects of cell sentience' section).…”

“…Furthermore, as mentioned above, the primary cilium can play a special role in response to the extracellular environment signals of the entire cell. In fact, it has been shown that signal detection by the primary cilium can modulate recognition/decoding apparatuses (such ion channels and receptors) located in other cell plasma membrane micro-domains (Singla and Reiter, 2006;Einstein et al, 2010;Christensen et al, 2012;Heng et al, 2014).…”