<scp>Sna</scp>3 Is an <scp>Rsp</scp>5 Adaptor Protein that Relies on Ubiquitination for Its <scp>MVB</scp> Sorting

<jats:p><jats:bold>The process in which ubiquitin (</jats:bold><jats:styled-content style="fixed-case"><jats:bold>Ub</jats:bold></jats:styled-content><jats:bold>) conjugation is required for trafficking of integral membrane proteins into multivesicular bodies (</jats:bold><jats:styled-content style="fixed-case"><jats:bold>MVBs</jats:bold></jats:styled-content><jats:bold>) and eventual degradation in the lumen of lysosomes/vacuoles is well defined. However</jats:bold>, <jats:styled-content style="fixed-case"><jats:bold>Ub</jats:bold></jats:styled-content><jats:bold>‐independent pathways into</jats:bold> <jats:styled-content style="fixed-case"><jats:bold>MVBs</jats:bold></jats:styled-content> <jats:bold>are less understood. To better understand this process, we have further characterized the membrane protein</jats:bold> <jats:styled-content style="fixed-case"><jats:bold>Sna</jats:bold></jats:styled-content><jats:bold>3, the prototypical</jats:bold> <jats:styled-content style="fixed-case"><jats:bold>Ub</jats:bold></jats:styled-content><jats:bold>‐independent cargo protein sorted through the</jats:bold> <jats:styled-content style="fixed-case"><jats:bold>MVB</jats:bold></jats:styled-content> <jats:bold>pathway in yeast. We show that</jats:bold> <jats:styled-content style="fixed-case"><jats:bold>Sna</jats:bold></jats:styled-content><jats:bold>3 trafficking to the vacuole is critically dependent on</jats:bold> <jats:styled-content style="fixed-case"><jats:bold>Rsp</jats:bold></jats:styled-content><jats:bold>5 ligase activity and ubiquitination. We find</jats:bold> <jats:styled-content style="fixed-case"><jats:bold>Sna</jats:bold></jats:styled-content><jats:bold>3 undergoes</jats:bold> <jats:styled-content style="fixed-case"><jats:bold>Ub</jats:bold></jats:styled-content><jats:bold>‐dependent</jats:bold> <jats:styled-content style="fixed-case"><jats:bold>MVB</jats:bold></jats:styled-content> <jats:bold>sorting by either becoming ubiquitinated itself or associating with other ubiquitinated membrane protein substrates. In addition, our functional studies support a role for</jats:bold> <jats:styled-content style="fixed-case"><jats:bold>Sna</jats:bold></jats:styled-content><jats:bold>3 as an adaptor protein that recruits</jats:bold> <jats:styled-content style="fixed-case"><jats:bold>Rsp</jats:bold></jats:styled-content><jats:bold>5 to cargo such as the methionine transporter</jats:bold> <jats:styled-content style="fixed-case"><jats:bold>Mup</jats:bold></jats:styled-content><jats:bold>1, resulting in efficient</jats:bold> <jats:styled-content style="fixed-case"><jats:bold>Mup</jats:bold></jats:styled-content><jats:bold>1 delivery to the vacuole</jats:bold>.</jats:p>