Membrane Proteins of the Endoplasmic Reticulum Induce High-Curvature Tubules

TLDR

The tubular endoplasmic reticulum is believed to be formed by integral membrane proteins, notably reticulons and the DP1/Yop1p family. Purified Yop1p and Rtn1p reconstituted into proteoliposomes formed narrow (~15–17 nm) tubules across various lipids, a process that depends on the central hydrophobic core and is disrupted by mutations that impair in vivo tubulation. These experiments demonstrate that individual reticulon and DP1/Yop1p proteins are sufficient to generate membrane tubules, with in vitro tubules being narrower than native ER due to higher protein concentration, suggesting that protein shape and oligomerization drive tubular ER formation.

Abstract

The tubular structure of the endoplasmic reticulum (ER) appears to be generated by integral membrane proteins, the reticulons and a protein family consisting of DP1 in mammals and Yop1p in yeast. Here, individual members of these families were found to be sufficient to generate membrane tubules. When we purified yeast Yop1p and incorporated it into proteoliposomes, narrow tubules (approximately 15 to 17 nanometers in diameter) were generated. Tubule formation occurred with different lipids; required essentially only the central portion of the protein, including its two long hydrophobic segments; and was prevented by mutations that affected tubule formation in vivo. Tubules were also formed by reconstituted purified yeast Rtn1p. Tubules made in vitro were narrower than normal ER tubules, due to a higher concentration of tubule-inducing proteins. The shape and oligomerization of the "morphogenic" proteins could explain the formation of the tubular ER.