Scd5p is an essential protein that colocalizes with cortical actin, and is required for cortical actin organization and endocytosis (6, 7, 3). Scd5p and the clathrin heavy- and light-chains (Chc1p & Clc1p) physically associate with Sla2p, a transmembrane actin-binding protein involved in membrane cytoskeleton assembly and cell polarization, which is also a homolog of the mammalian huntingtin interacting protein HIP1 and the related HIP1R (6). Both Scd5p and clathrin are required for Sla2p localization at the cell cortex (6).

Scd5p activity appears to be phospho-regulated. Scd5p is phosphorylated by Prk1p, which results in its negative regulation, and dephosphorylated by the Glc7p type-1 protein phosphatase, which relieves this inhibition (7, 3, 8). Mutations in GLC7 that disrupt Glc7p interactions with Scd5p result in defects in endocytosis and actin organization (7, 3, 8).

Scd5p was first identified from a genetic screen searching for multicopy suppressors of defects seen in cells depleted of Chc1p (5). Loss of function scd5 mutants display defects in receptor-mediated endocytosis, fluid-phase endocytosis, and normal actin organization, and contain larger and depolarized cortical actin patches and a prevalence of G-actin bars, also known as monomeric actin (6, 3). Cells expressing truncated Scd5p (Scd5p-delta338) accumulate an internal pool of fully glycosylated Suc2p invertase and mature alpha-factor (1). This phenotype was originally interpreted as a problem with protein secretion, but was later shown to be caused by defects in receptor-mediated endocytosis, similar to that seen in clathrin mutants (1, 6). Overexpression of SCD5 partially suppresses the actin defects of both chc1 and clc1 nulls (6).

Last updated: 2005-10-18