PMID: 11983428

 

    Legend: Sugar

Title : Stromal interaction molecule 1 ( STIM1 ), a transmembrane protein with growth suppressor activity, contains an extracellular SAM domain modified by N-linked glycosylation

Abstract :

1. Stromal interaction molecule 1 ( STIM1 ) is a cell surface transmembrane glycoprotein implicated in tumour growth control and stromal-haematopoietic cell interactions
2. A single sterile alpha motif ( SAM ) protein- protein interaction domain is modelled within its extracellular region , a subcellular localisation not previously described for other SAM domain-containing proteins
3. We have defined the transmembrane topology of STIM1 by determining the sites of N-linked glycosylation
4. We have confirmed that STIM1 is modified by N-linked glycosylation at two sites within the SAM domain itself, deduced as asparagine residues N131 and N171 , demonstrating that STIM1 is translocated across the membrane of the endoplasmic reticulum such that the SAM domain resides within the endoplasmic reticulum (ER) lumen
5. Both N-linked oligosaccharides remain endoglycosidase H-sensitive, indicating absence of full processing within the ER and Golgi
6. This immature modification is nevertheless sufficient and critical for cell surface expression of STIM1
7. We show that STIM1- STIM1 homotypic interactions are mediated via the cytoplasmic rather than the extracellular region of STIM1 , excluding an essential role for the SAM domain in these protein interactions
8. These studies provide the first evidence for an extracellular localisation of a SAM domain within any protein , and the first example of a SAM domain modified by N-linked glycosylation