High impact information on PAN1

• We suggest that Pan1p forms the core of an endocytic complex and physically couples actin polymerization nucleated by the Arp2/3 complex to the endocytic machinery, thus providing the forces necessary for endocytosis [1].
• Here we show that the yeast endocytic protein Pan1p binds to and activates the Arp2/3 complex [1].
• In vitro phosphorylation assays demonstrate that Prk1p is able to phosphorylate regions of Pan1p containing the LxxQxTG repeats, including the region responsible for binding to End3p [2].
• Normal actin cytoskeleton organization in budding yeast requires the function of the Pan1p/ End3p complex [2].
• By screening for mutations that can suppress the temperature sensitivity of a pan1 mutant (pan1-4), a novel serine/threonine kinase Prk1p is now identified as a new factor regulating the actin cytoskeleton organization in yeast [2].

Biological context of PAN1

• Mutations in PAN1 and END3 cause defects in the organization of actin cytoskeleton and endocytosis [2].
• The Pan1 protein contains an EF-hand calcium-binding domain, a putative Src homology 3 (SH3)-binding domain, a region similar to the actin cytoskeleton assembly control protein Sla1, and two repeats of a newly identified protein motif known as the EH domain [3].
• In vitro binding studies using GST fusion proteins and yeast extracts defined distinct binding sites on yAP180A for Pan1p and clathrin. yAP180 proteins and Pan1p, like actin, localize to peripheral patches along the plasma membrane [4].
• These results indicate that the functions of Pan1p, End3p, and Sla1p in cell wall morphogenesis may depend on the formation of a heterotrimeric complex [5].
• We found that the most severe phenotypes, with blocked endocytosis and aggregated actin, required expression of nearly full length Pan1p, and also required the endocytic regulatory protein kinase Prk1p [6].

Anatomical context of PAN1

• Phosphorylated Pan1p is probably then dephosphorylated in the cytosol [7].
• Pan1p is a homologue of the mammalian protein eps15, which has been implicated in endocytosis by virtue of its association with the plasma membrane clathrin adaptor complex AP-2 [4].
• These cell wall defects are also exhibited by wild-type cells overproducing the C-terminal region of Sla1p that is responsible for interactions with Pan1p and End3p [5].

Associations of PAN1 with chemical compounds

• We observed genetic interactions between the yeast SJL1 gene and PAN1, which suggest a role for phosphoinositide metabolites in Pan1p function [4].
• Pan1p, an actin cytoskeleton-associated protein, is required for growth of yeast on oleate medium [8].
• Pan1p, which binds several other endocytic proteins, is composed of multiple protein-protein interaction domains including two Eps15 Homology (EH) domains, a coiled-coil domain, an acidic Arp2/3-activating region, and a proline-rich domain [6].

Co-localisations of PAN1

• Immunofluorescence staining revealed that the Pan1 protein colocalized with the cortical actin patches, suggesting that it may be a filamentous actin-binding protein [3].
• Immunoprecipitation experiments confirmed that Rsp5p and Act1p colocalize in pan1 mutants [9].

Regulatory relationships of PAN1

• Synthetic growth defects were observed in a pan1-20 ENT1(EE) double mutant, suggesting that Ent1p phosphorylation negatively regulates the formation/activity of a Pan1p-Ent1p complex [10].
• Overall, our results establish that Sla2p's regulation of Pan1p plays an important role in controlling Pan1p-stimulated actin polymerization during endocytosis [7].
• Pan1p activity is negatively regulated by Prk1 kinase phosphorylation after endocytic internalization [7].
• Interestingly, Sla2p specifically inhibited Pan1p Arp2/3 complex activation activity in vitro [7].

Other interactions of PAN1

• The suppression of pan1-4 by prk1 requires the presence of mutant Pan1p [2].
• MDP3 is identical to PAN1, which encodes a protein involved in initiation of translation and actin cytoskeleton organization [11].
• Yeast Eps15-like endocytic protein, Pan1p, activates the Arp2/3 complex [1].
• This new screening strategy demonstrates a role for She4p and Pan1p in endocytosis, and provides a new general method for the identification of additional endocytosis mutants [12].
• These data confirm that Pan2p and not Pan1p is required for PAN activity, and they suggest that ribonucleases other than the Pab1p-stimulated PAN are capable of shortening poly(A) tails in vivo [13].

Analytical, diagnostic and therapeutic context of PAN1

• Sequence analysis revealed the presence of 17 open reading frames (ORFs), four of them previously known yeast genes (sly12, pan1, sts1 and prl1), a tRNA gene and the centromere motif [14].

References