Global Effects Of RAB3GAP1 Dysexpression On The Proteome Of Mouse Cortical Neurons

Objective: Mounting studies have demonstrated that RAB3GAP1 expression is modified in brain diseases with multiple neurobiological functions and processes and acts as a potentially significant target.However,the cellular and molecular events arising from RAB3GAP1 dysexpression are still incompletely understood.To more thoroughly understand the regulatory mechanism of Rab3GAP1 as a significant disease target,it may be required to comprehensively investigate protein expression aberrations arising from Rab3GAP1 dysregulation.Methods: In this work,underexpression and overexpression of RAB3GAP1 were first induced into cultured mouse cortical neurons by transfection with lentivirus plasmids.Further parallel reaction monitoring(PRM)analysis illustrated that Sub1,Ssrp1,and Top1 proteins might serve as new potentially important linkers in the RAB3GAP1-mediated autophagy pathway in the cortical neurons.Further parallel reaction monitoring(PRM)analysis explored the global effects of RAB3GAP1 dysexpression on the proteome of mouse cortical neurons.Results: A total of 364 proteins in the RAB3GAP1-underexpression group and 314 proteins in the RAB3GAP1-overexpression group were identified to be differentially expressed.Subsequent bioinformatics analysis indicated that the proteome functional expression profiles induced by RAB3GAP1 underexpression and overexpression were different,suggesting the potential differences in biological processes and cellular effects.Subsequent intergroup cross-comparison revealed some candidate target proteins regulated directly by RAB3GAP1.According to further PRM analysis,it is tempting to speculate that Sub1,Ssrp1,and Top1 may be some new potential important linkers in the RAB3GAP1-mediated autophagy pathway in the cortical neurons.Conclusion: Sub1,Ssrp1 and Top1 may be some new potential important linkers in RAB3GAP1-medicated autophagy pathway in the cortical neurons.Also,in the present study the expression level of Krt77 as cytoskeletal proteins was found to be closely correlated with RAB3GAP1 dysexpression.To some extent,it could be speculated that Krt77 protein might be involved in RAB3GAP1-regulated axonal transport.However,these molecular mechanisms particularly in respect to RAB3GAP1-based autophagy required further investigation in the future study.