한빛사논문
- 조회513
Paul Jongseo Lee,1,3,4 Yu Sun,1,4 Alexa R. Soares,2,3 Caroline Fai,2 Marina R. Picciotto,2,3 and Junjie U. Guo 1,3,5,*
1Department of Neuroscience, Yale University School of Medicine, New Haven, CT 06510, USA
2Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06508, USA
3Interdepartmental Neuroscience Program, Yale University, New Haven, CT 06520, USA
4These authors contributed equally
5Lead contact
*Corresponding author: correspondence to Junjie U. Guo
Abstract
While many mRNAs contain more than one translation initiation site (TIS), the functions of most alternative TISs and their corresponding protein isoforms (proteoforms) remain undetermined. Here, we showed that alternative usage of CUG and AUG TISs in neuronal pentraxin receptor (NPR) mRNA produced two proteoforms, of which the ratio was regulated by RNA secondary structure and neuronal activity. Downstream AUG initiation truncated the N-terminal transmembrane domain and produced a secreted NPR proteoform sufficient in promoting synaptic clustering of AMPA-type glutamate receptors. Mutations that altered the ratio of NPR proteoforms reduced AMPA receptors in parvalbumin-positive interneurons and affected learning behaviors in mice. In addition to NPR, upstream AUU-initiated N-terminal extension of C1q-like synaptic organizers anchored these otherwise secreted factors to the membrane. Together, these results uncovered the plasticity of N-terminal signal sequences regulated by alternative TIS usage as a potentially widespread mechanism in diversifying protein localization and functions.
논문정보
- Research article
- 2024년 09월 (BRIC 등록일 2024-09-25)
- 국외 연구진
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