SGD Paper 
Balcer HI, et al. (2010) The p40/ARPC1 Subunit of Arp2/3 Complex Performs Multiple Essential Roles in WASp-regulated Actin Nucleation. J Biol Chem 285(11):8481-91
Abstract: The Arp2/3 complex is a conserved seven-subunit actin-nucleating machine activated by Wiskott Aldrich Syndrome protein (WASp). Despite its central importance in a broad range of cellular processes, many critical aspects of the mechanism of Arp2/3 complex have yet to be resolved. In particular, some of the individual subunits in the complex have not been assigned clear functional roles, including p40/ARPC1. Here, we dissected the structure and function of S. cerevisiae p40/ARPC1, which is encoded by the essential ARC40 gene, by analyzing 39 integrated alleles that target its conserved surfaces. We identified three distinct sites on p40/ARPC1 required for function in vivo: one site contacts p19/ARPC4, one contacts p15/ARPC5, and one site resides in an extended structural arm of p40/ARPC1. Using a novel strategy, we purified the corresponding lethal mutant Arp2/3 complexes from yeast and compared their actin nucleation activities. Lethal mutations at the contact with p19/ARPC4 specifically impaired WASp-induced nucleation. In contrast, lethal mutations at the contact with p15/ARPC5 led to unregulated (leaky) nucleation in the absence of WASp. Lethal mutations in the extended arm drastically reduced nucleation, and the same mutations disrupted the ability of purified p40/ARPC1 arm domain to bind the VCA domain of WASp. Together, these data indicate that p40/ARPC1 performs at least three distinct, essential functions in regulating Arp2/3 complex-mediated actin assembly: (1) suppression of spontaneous nucleation by Arp2/3 complex, which requires proper contacts with p15/ARPC5; (2) propagation of WASp-activation signals via contacts with p19/ARPC2; and (3) direct facilitation of actin nucleation through interactions of the extended arm with the VCA domain of WASp.
| Status: Published | Type: Journal Article | PubMed ID: 20071330 |
Topics addressed in this paper
Number of different genes curated to this paper: 7
- To find other papers on a gene and topic, click on the colored ball in the appropriate box.
- displays other papers with information about that topic for that gene.
- displays other papers in SGD that are associated with that topic.
The topic is addressed in these papers but does not describe a specific gene or chromosomal feature.
- To go to the Locus page for a gene, click on the gene name.
| Topics | Genes linked to topics | ||||||
|---|---|---|---|---|---|---|---|
| ACT1 | ARC15 | ARC19 | ARC40 | ARP2 | ARP3 | LAS17 | |
| Additional Literature |  | | | | | ||
| Function/Process | | | |||||
| Fungal Related Genes/Proteins | | ||||||
| Mutants/Phenotypes | | ||||||
| Non-Fungal Related Genes/Proteins | | ||||||
| Primary Literature | | | |||||
| Protein Physical Properties | | ||||||
| Protein Sequence Features | | ||||||
| Protein-protein Interactions | | | | | |||
| Protein/Nucleic Acid Structure | | | | ||||
| Regulation of | | ||||||
| Strains/Constructs | | | |||||
| Techniques and Reagents | | ||||||
