Communications Center

Every life-sustaining biological process requires dedicated protein molecules. Proteins allow us to move, breathe, eat, and even read this sentence. To perform these functions, proteins must first reach their correct destinations within a cell. When proteins malfunction or fail to reach their destinations, diseases including diabetes, dementia, and cancer can arise.

Many proteins enter a cellular compartment called the endoplasmic reticulum by passing through microscopic channels called translocons. Like tunnels carved through a mountain, translocons allow proteins to travel from where they are made to where they will perform their cellular jobs. Occasionally, however, a protein stalls and becomes stuck while passing through a translocon. Similar to a car crash blocking the entrance to a highway tunnel, one stalled protein can prevent many others from reaching their destinations.

Fortunately, cells possess molecular “tow trucks” that help clear these blockages. Students in the Rubenstein laboratory previously discovered that two proteins, Hrd1 and Ste24, function in parallel pathways to clear clogged translocons. However, the molecules that assist these cellular tow trucks remained unclear.

In this presentation, I will describe my lab’s recent discovery that a protein called Dfm1 assists the Ste24 tow truck to remove blockages, allowing other proteins to get to where they need to be to do their jobs. Cells lacking Dfm1 are unable to efficiently remove clogging proteins from translocon channels and are hypersensitive to a translocon-clogging protein associated with pancreatic dysfunction in type 2 diabetes.

Together, our findings identify Dfm1 as an important member of the cellular tow truck crew and provide new insight into how cells protect themselves from clogged protein channels. Understanding these protective pathways may inform new approaches for combating diseases associated with blocked translocons.