The ER Anchoring and Abundance of the EEF1B Complex is Affected by Tissue Specific Alternative EEF1D Spicing

Among its components, EEF1D undergoes alternative splicing to produce one long and several short isoforms, each with distinct N-terminal domains and tissue-specific expression patterns. Although the short isoforms are broadly expressed, their functional significance has remained unclear.

In this study, we show that short EEF1D isoforms containing exon 5 interact with endoplasmic reticulum (ER)-resident scaffold protein KTN1 and RRBP1, thereby anchoring the EEF1B complex to the ER. Mass spectrometry of FLAG-tagged EEF1D identified these interactions, and deletion of exon 5 disrupted ER anchoring, resulting in diffuse cytoplasmic localization of the EEF1B complex. In exon 5 knockout mice, this altered localization was accompanied by reduced EEF1B subunit abundance in multiple tissues, including liver, although global protein synthesis rates remained unaffected.