High impact information on SLA2

• In cells lacking the highly conserved endocytic protein Sla2p, patch motility was arrested and actin comet tails associated with endocytic patch complexes [1].
• However, yeast mutant strains defective in endocytosis (end3, end4 and chc1-ts) and vacuolar degradation (pep4) exhibit copper-dependent Ctr1p degradation, indicating that internalization and delivery to the vacuole is not the principal mechanism responsible for degradation [2].
• An end4 mutation, isolated for its defect in the endocytic uptake of alpha-factor pheromone (Raths, S., J. Rohrer, F. Crausaz, and H. Riezman. 1993. J. Cell Biol. 120:55-65), blocks constitutive endocytosis of the a-factor receptor, yet fails to block ubiquitination of the receptor [3].
• Null mutations in SLA1 and SLA2 cause temperature-sensitive growth defects [4].
• In addition, synthetic-lethal interactions were observed for double-mutants containing null alleles of SLA2 and SAC6 [4].

Biological context of SLA2

• Mutations in SLA1 or SLA2, which alter actin cytoskeleton architecture, induced a conditional synthetic lethal phenotype in combination with doa4-10 in the absence of DNA damage [5].
• Sla2p is required for cellular morphogenesis and polarization of the cortical cytoskeleton [4].
• The N-terminal domain of End4p is required for growth at high temperature, endocytosis, and actin organization [6].
• Three of the four mutants (mrt4, grc5, and sla2) were not defective in protein synthesis, suggesting that these strains contain mutations in factors that may play a specific role in mRNA decay [7].
• We report the complete nucleotide sequence of SLA2 of the dimorphic yeasts Candida albicans and Yarrowia lipolytica [8].

Anatomical context of SLA2

• Synthetic-lethal interactions identify two novel genes, SLA1 and SLA2, that control membrane cytoskeleton assembly in Saccharomyces cerevisiae [4].
• MOP2 (SLA2) affects the abundance of the plasma membrane H(+)-ATPase of Saccharomyces cerevisiae [9].
• The COOH terminus of Sla2p contains a 200 amino acid region with homology to the COOH terminus of talin, a membrane cytoskeletal protein which is a component of fibroblast focal adhesions [4].
• Defects in cell wall morphology, accumulated vesicles, and protein secretion kinetics were found in sla2 mutants similar to defects found in act1 mutants [10].
• Vesicles that accumulate in the sla2 and act1 mutants are immunoreactive with antibodies directed against the small GTPase Ypt1p but not with antibodies directed against the homologous Sec4p found on classical "late" secretory vesicles [10].

Associations of SLA2 with chemical compounds

• A liposome-binding assay revealed that Sla2p binds to PtdIns(4,5)P2 specifically through its ANTH domain and identified specific lysine residues required for this interaction [11].
• Ligand-mediated repression of spermidine transport was delayed in end3 and end4 mutants that are deficient in the initial steps of the endocytic pathway, and spermidine uptake activity was increased 4- to 5-fold in end3 mutants relative to parental cells, although the stability of the transport system was similar in both strains [12].
• Generation of an Deltasla1Deltasla2 double mutant demonstrates that Sla2p is likely to act upstream of Sla1p in endocytosis, whereas sensitivity to latrunculin-A suggests that the proteins have opposite effects on actin dynamics [13].

Physical interactions of SLA2

• End4p/Sla2p interacts with actin-associated proteins for endocytosis in Saccharomyces cerevisiae [6].

Regulatory relationships of SLA2

• Interestingly, Sla2p specifically inhibited Pan1p Arp2/3 complex activation activity in vitro [14].
• An interaction between Sla1p and Sla2p plays a role in regulating actin dynamics and endocytosis in budding yeast [13].

Other interactions of SLA2

• Mutant alleles of three genes, DOA4, SLA1 and SLA2, were recovered [5].
• (iii) Rsp5p and Sla2p coimmunoprecipitate and partially colocalize to punctate structures in wild-type cells [15].
• Negative Regulation of Yeast Eps15-like Arp2/3 Complex Activator, Pan1p, by the Hip1R-related Protein, Sla2p, during Endocytosis [14].
• Modifier of pma1 (mop) mutants were isolated as enhancers of the mutant phenotypes of pma1 mutants. mop2 mutations reduce the abundance and activity of Pma1 protein on the plasma membrane without affecting the abundance of other prominent plasma membrane proteins [9].
• Patches that do internalize receive Sla1p late, which is followed by Abp1, which appears near the end of Sla2p lifetime [16].

Analytical, diagnostic and therapeutic context of SLA2

• Sequence analysis of SLA2 of the dimorphic yeasts Candida albicans and Yarrowia lipolytica [8].
• Sequence alignments and secondary structure predictions verified that mHip1R belongs to the Sla2 protein family [17].
• Using immunofluorescence microscopy, Rpg1p and Sla2p proteins were colocalized at the patch associated with the tip of emerging bud [18].
• Using live cell imaging techniques to visualize endocytic vesicle formation, we find that the N-terminal Sla2p binding region of LC promotes the progression of arrested Sla2p patches that form in the absence of HC [19].

References