Neuropilin-1 promotes Hedgehog signaling through a novel cytoplasmic motif

Pinskey, Justine M; Franks, Nicole E.; McMellen, Alexandra; Giger, Roman J.; Allen, Benjamin L.

doi:10.1074/jbc.m117.783845

Cited by 19 publications

(40 citation statements)

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“…DRG neurons have been widely used to decipher molecular mechanisms of axonal outgrowth, axon guidance, and branching in vitro [ 56 , 57 , 58 ]. Interestingly, some of the major guidance receptors, such as Robo1 and Neuropilin-1, have recently been localized to the primary cilium of neurons in the CNS and mouse fibroblasts, respectively [ 43 , 59 ]. Hence, it is possible that some of the signaling pathways involved in axonal development might be transduced at the primary cilium level.…”

Section: Discussionmentioning

confidence: 99%

Investigating Primary Cilia during Peripheral Nervous System Formation

Yusifov

Dumoulin

Stoeckli

2021

IJMS

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The primary cilium plays a pivotal role during the embryonic development of vertebrates. It acts as a somatic signaling hub for specific pathways, such as Sonic Hedgehog signaling. In humans, mutations in genes that cause dysregulation of ciliogenesis or ciliary function lead to severe developmental disorders called ciliopathies. Beyond its role in early morphogenesis, growing evidence points towards an essential function of the primary cilium in neural circuit formation in the central nervous system. However, very little is known about a potential role in the formation of the peripheral nervous system. Here, we investigate the presence of the primary cilium in neural crest cells and their derivatives in the trunk of developing chicken embryos in vivo. We found that neural crest cells, sensory neurons, and boundary cap cells all bear a primary cilium during key stages of early peripheral nervous system formation. Moreover, we describe differences in the ciliation of neuronal cultures of different populations from the peripheral and central nervous systems. Our results offer a framework for further in vivo and in vitro investigations on specific roles that the primary cilium might play during peripheral nervous system formation.

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Section: Discussionmentioning

confidence: 99%

Investigating Primary Cilia during Peripheral Nervous System Formation

Yusifov

Dumoulin

Stoeckli

2021

IJMS

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“…Before presenting those evidences, we should give some information about hedgehog (HH) signaling. Briefly, HH signaling is essential for tissue patterning and organ formation during embryonic and postnatal development, as well as in cancer development and tissue homeostasis renewal and repair in adult animals [68]. The HH pathway acts via activation of transcriptional effectors, such as the glioblastoma (Gli) proteins, a family of transcription factors whose target genes remain enigmatic.…”

Section: Neuropilins and The Primary Ciliummentioning

confidence: 99%

“…Referring to the primary cilium, studies conducted by Pinskey et al [68] found that NRP1 and NRP2 promote the activation of Gli transcription factor. Interestingly, the authors found that a conserved 12 amino acid region of the NRP1 cytoplasmic domain between amino acids 890 and 902 is responsible for the HH-signal promotion.…”

Section: Neuropilins and The Primary Ciliummentioning

confidence: 99%

“…Interestingly, the authors found that a conserved 12 amino acid region of the NRP1 cytoplasmic domain between amino acids 890 and 902 is responsible for the HH-signal promotion. Considering that an intact primary cilium is a main component of the HH signaling, they also looked for the localization of NRP1 in this subcellular compartment and showed the unique evidence until now about the localization of NRP1, but not NRP2, in the primary cilium [68]. Despite the fact that the localization of NRP1 in the primary cilium was not required for HH signaling promotion, it is intriguing why NRP1 is present in primary cilium and what would be its physiological relevance there.…”

Section: Neuropilins and The Primary Ciliummentioning

confidence: 99%

See 1 more Smart Citation

Sensing Fluid-Shear Stress in the Endothelial System with a Special Emphasis on the Primary Cilium

Rezgaoui¹,

Rodríguez²,

Herlitz³

et al. 2018

Endothelial Dysfunction - Old Concepts and New Challenges

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Fluid shear stress (FSS) is able to generate phenotypic changes in the cells in direct contact with the strain force. In order to detect and transduce FSS into intracellular pathways, biological systems use a specific set of sensors, called mechanosensors. The process involves the conversion of the mechanical force into a chemical or electrical signal. Primary cilium is a non-motile organelle that emanates from the cell surface of most mammalian cell types that act as a mechanosensor. Increasing evidence suggests that primary cilia are key coordinators of signaling pathways in tissue homeostasis and when defective may cause human diseases and developmental disorders. Here, we will describe the endothelial primary cilium as a mechanotransductory organelle sensing FSS. To fulfill this function, primary cilium requires the localization of mechanoproteins, polycystin-1 and-2, in their membrane and the structural gene product, polaris. Physiologically, deflection of primary cilium increases the intracellular calcium concentration triggering a signaling pathway that leads to nitric oxide (NO) formation and vasodilation. Additionally, ciliopathies, such as polycystic kidney disease and atherosclerosis, will also be discussed. We also analyze available information regarding a trio of membrane receptors involved in FSS sensing and transducing such as vascular endothelial growth factor receptors (VEGFRs) and its coreceptor neuropilin (NRP), as well as purinergic receptors (P2Y2). Whether or not they modulate, the primary cilium role in sensing FSS is poorly understood. This chapter highlights the main relevance of primary cilium in sensing blood flow, although exact mechanisms are not fully known yet.

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“…[11][12][13][14] The mechanisms for the role of NRP-1 in cancer progression rely on its interactions with several key signalling pathways in cancer cells, such as transforming growth factor β1 (TGFβ1), semaphorin (Sema), vascular endothelial growth factor (VEGF), hedgehog (HH), interferon-γ (IFNγ) and GAIP/RGS19-interacting protein (GIPC1). [15][16][17][18][19][20] Therefore, targeting NRP-1 has been shown to be a potential therapeutic target for some cancers. 21,22 However, the role of NRP-1 in GBC remains unclear.…”

Section: Introductionmentioning

confidence: 99%