Abstract
The G-protein coupled receptor Smoothened (SMO) is the main signal transducer of the Hedgehog signaling pathway. The activity of SMO can be classified as the canonical pathway which proceeds through the activation of the GLI-family of transcription factors to activate transcription of the Hedgehog target genes, and the non-canonical pathway which proceed through recruitment and activation of trimeric G-proteins. Previously, we have shown the involvement of non-canonical SMO activity in sustaining cell survival signaling, and recycling/degradation endosomal sorting of receptor tyrosine kinases. In an attempt to investigate novel SMO (non-canonical) biology we decided to explore the SMO interactome through the application of Live-Cell BioID. Our efforts identify the lipid binding and transport protein, TMEM24, as a putative interaction partner to SMO. TMEM24 is involved in the transport of PI directly from the ER, where it is being synthesized, to the plasma membrane for further conversion into signaling molecules PIP2 (and PIP3). Evidently, SMO is involved in the direct transport of signaling molecules precursor PI, through the transcriptional regulation of TMEM24.