Analysis Of The Role Of SNARE Proteins In Secretory And Autophagic Routes In Drosophila

Cancer and neurodegenerative diseases have become essential factors threatening human health.Blocked vesicle fusion is associated with many cancers and neurodegenerative diseases.SNARE proteins serve as critical regulators of vesicle fusion.Its protein secretion and autophagy-related membrane fusion are involved in the occurrence and development of related diseases.However,how SNARE and other proteins regulate this process and its molecular mechanism remains unclear.In this study,I systematically studied all 25 members of the SNARE protein family in Drosophila melanogaster.First,the expression of SNARE proteins was knocked down by RNAi technology,and the SNARE genes related to collagen secretion and autophagy were screened out.Secondly,essential SNARE proteins were co-localized with markers of the endoplasmic reticulum exit site,Golgi apparatus,and lysosome,respectively,and their distribution was analyzed.Finally,further exploring the key SNARE proteins Syx1,Syx4,Syx7,Syx17,Snap29,and Ykt6,I found that Syx1 and Syx4 are functionally redundant.Syx1/Syx4 and Sec1/Munc18 protein Rop participate in the Rab11(Rab protein)-mediated traffic.At the same time,Syx7 interacts with another Sec1/Munc18 protein,Slh,and participates in the Rab11-mediated secretion pathway.Syx7,Syx17,Snap29,and Ykt6 form different combinations of SNARE complexes to mediate the fusion of autophagosomes and lysosomes.Syx7 also plays a role in collagen secretion and autophagy-related membrane fusion.In addition,the simultaneous knockdown of Syx1 and Syx4 caused mainly trans-Golgi enlargement.However,the knockdown of Syx7,Syx17,Snap29,and Ykt6 resulted in significantly enlarged trans-Golgi around the nucleus.These results suggest that SNARE proteins are essential in maintaining transGolgi architecture.In summary,these findings reveal multiple pathways in which SNARE proteins,Sec1/Munc18 proteins,and Rab proteins mediate protein secretion and autophagy-related membrane fusion.At the same time,it provides a good model for studying protein secretion and autophagy-related membrane fusion in vivo.We can better understand the interaction between organelles in vesicle fusion through the systematic and in-depth study of SNARE proteins.The abnormality of SNARE protein function is a potential factor leading to many diseases,and SNARE and its related regulatory proteins can be used as new drug targets.These studies provide fresh ideas and insights for treating associated diseases caused by impaired vesicle fusion.