Hedgehog Signaling Pathway in Vertebrates | Purpose and Mechanism

hey everyone in this lesson we talked about the head chuckling pathway in vertebrates now in a pretty position we talked about this pathway in invertebrates but in this lesson around talk about the vertebrate pathway and we're gonna talk about the differences between vertebrates and invertebrates with regards to the Hedgehog signaling pathway so to begin the Hedgehog signaling pathway in vertebrates is involved in embryological development just like it was or just like it is in Hedgehog signaling in invertebrates and in invertebrates Hedgehog signaling is involved in controls development patterning tissue growth and meadow genesis specifically of the cerebellum and retina and it also controls homeless aces in tissue repair of adult neural stem cells and it has other functions in axon guidance in other roles as well now we mentioned a couple concepts in the invertebrate Hedgehog signaling video one of those concepts was graded signaling and that means that different gradients of Hedgehog protein induced different subsets of genes so that means that gee certain genes are activated at certain threats thresholds of Hedgehog protein and that really relates to different concentrations of Hedgehog protein that are exposed to a cell lead to different levels of intracellular signaling and in the cell can detect that different level of intracellular signaling to activate certain genes in response and the other concept was this idea of organ tissue specific gene induction which means that Hedgehog proteins induce different genes in different organs and tissue so if it's in the arms as opposed to the brain there's different genes that are activated so all of this sounds extremely familiar to what we've learned already in invertebrates so what are some of the differences what are some of the differences between vertebrate and invertebrate hedgehogs England well in vertebrates Hedgehog signaling occurs in a primary cilium of the cell secondly we've talked about sea proteins in invertebrates but these sea proteins are actually known as proteins invertebrates and these Glee proteins within vertebrate animals are more specialized so for example Glee 2 is more utilized as an activator or a transcriptional activator and Glee 3 is usually more utilized as a repressor of transcriptional activity so again the Hedgehog signaling pathway in vertebrates occurs within a primary cilium so that means that this primary cilium has microtubules associated with it there is also another protein known as g PR 161 and we've talked about patched before patched is also involved in vertebrate Hedgehog signaling and smoothened is also involved in vertebrate Hedgehog signaling so smoothened is located within with usually within an endosome within the cell so when there's no Hedgehog proteins present the Hedgehog signaling pathway is considered inactivated and when it's in inactivated patched inhibits smoothened and one when smoothing is inhibited it cannot enter into the plasma membrane which means that smooth and resides in the cytosol usually within an endosome also when this pathway is inactivated Glee proteins like Glee 2 and Glee 3 are associated with sufu protein we've talked about this protein in the invertebrate Hedgehog singling the lesson in when in activated proteins cki protein kinase a and glycogen synthase kinase 3 beta or GSK 3 beta all phosphorylate Glee proteins and when these Glee proteins are phosphorylated they are processed by the proteasome and they're actually cleaved into a truncated version of themselves so Glee 2 gets actually truncated or chopped into a smaller piece of Glee 2r and Glee 3 gets truncated into glee 3r these are the repressor forms of these proteins these Glee two are in glee three are proteins these repressor proteins can then translocate into the nucleus where they can inhibit transcriptional activation of Hedgehog mediated genes when this pathway is activated when there are Hedgehog proteins present such as sonic hedgehog or sh h hedgehog proteins like sonic hedgehog can bind and inhibit patched and the binding of sonic hedgehog to patched is facilitated and promoted by proteins such as CD o brother of CDO or BOC gas one in lrp two so these other proteins CEO BOC gas one in lmp2 all promote and facilitate the binding of sonic hedgehog to patched in order to four hedgehog to inhibit patched so once patch is inhibited patch can no longer inhibit smoothen and in fact when sonic hedgehog vines to patched g both GPR 161 and patch will actually leave the membrane of the primary cilium and be degraded within a proteasome inside the cell without patched smooth and is no longer inhibited and smooth and will be phosphorylated by both c ki and g PR k2 when smoothen has been phosphorylated by both GPR k2 and c ki with the help of microtubule motor kif 3a and beta arrestin smooth and can then enter into the plasma membrane of the primary cilium and it enters into areas of the primary cilium membrane in close association with another protein known as EB C when smooth and is within the membrane of the primary cilium kif's seven aids in the movement of both Glee proteins and sufu proteins through the primary cilium and at this point Glee proteins disassociate from sufu so they no longer bind to each other so when Glee proteins are not associated with sufu proteins and when the Glee proteins are within the primary cilium they are not phosphorylated by those protein kinase as we mentioned earlier which means that the Glee proteins are not phosphorylated and which means that they are not processed by the proteasome and they can remain in their full form so as opposed to the repress reforms Glee 2 are in Glee three are the Glee proteins are now on their full form Glee 2 and Glee 3 which means that in their full form Glee 2 in Glee 3 can then translocate and enter into the nucleus where they can bind to the DNA and induce the expression of Glee target genes and these Glee target genes are responsible for development patterning and differentiation and some of those other roles that we mentioned earlier like homeostasis as well so again when the Hedgehog signaling pathway is inactivated Glee proteins are proteolytically cleaved to their Glee are forms and those Glee are forms can enter the nucleus and inhibit transcriptional activation but when the hedgehog pathway is activated when there are Hedgehog proteins present the Glee proteins are not proteolytically processed into their art form and they remain in their normal full forms and they can then enter the nucleus in activate Glee target genes so that is the difference between the inactivated and activated Hedgehog signaling in vertebrates anyways guys that was a lesson on Hedgehog signaling in vertebrates I hope you found this video helpful if you did please like and subscribe for more videos like this one and as always thank you so much for watching and I'll see you next time

Channel: JJ Medicine

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Keywords: Hedgehog Signaling, Hedgehog Signalling, Hedgehog signaling pathway, Hedgehog signalling pathway, Hedgehog signaling cascade, Hedgehog signaling in vertebrates, Vertebrate hedgehog signaling, Hedgehog signaling animation, Hedgehog signalling pathway animation, Hedgehog signaling pathway animation, Hedgehog signaling primary cilium, Hedgehog signaling pathway review, hedgehog signaling lesson, hedgehog pathway, hedgehog signaling pathway cancer, hedgehog pathway animation

Id: fzVcJ7fWrVg

Length: 8min 34sec (514 seconds)

Published: Sun Mar 18 2018