A novel endoplasmic reticulum export signal: Proline at the +2-position from the signal peptide cleavage site

Yoshinori Tsukumo, Satomi Tsukahara, Sakae Saito, Takashi Tsuruo, Akihiro Tomida

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)

Abstract

NUCB1 (nucleobindin 1) is a Golgi-localized soluble protein with a signal peptide and multiple functional domains. We reported recently that NUCB1 is a negative regulator of the unfolded protein response that activates various endoplasmic reticulum (ER)-originating signaling pathways. In that report, we also showed that Golgi localization of NUCB1 was essential to regulate the unfolded protein response. However, the localization mechanism of NUCB1 is still unknown. Here, we report that the proline residue at the +2-position (Pro+2) from the signal peptide cleavage site is the determinant of NUCB1 protein export from the ER and subsequent transport to the Golgi. Fusion of the N-terminal amino acids 1-35 peptide region, including both signal peptide (amino acids 1-26) and Pro+2, was sufficient for enhanced green fluorescent protein to localize in the Golgi, whereas single amino acid mutation of Pro+2 resulted in defective export from the ER without affecting the protein maturation process. Furthermore, we demonstrated that Pro+2 was important for the enhanced green fluorescent protein fusion protein to concentrate at a transport vesicle formation site within the ER, often termed the ER exit site. Interestingly, such a Pro+2 has also been functionally conserved in other Golgi-localized soluble proteins, Cab45 (Ca2+-binding protein of 45 kDa), reticulocalbin 1, and calumenin. Our findings indicate that Pro+2 can function as a novel ER export signal of some Golgi proteins.

Original languageEnglish
Pages (from-to)27500-27510
Number of pages11
JournalJournal of Biological Chemistry
Volume284
Issue number40
DOIs
Publication statusPublished - 2009 Oct 2
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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