Myosin-driven peroxisome partitioning inS. cerevisiae

Abstract

In Saccharomyces cerevisiae, the class V myosin motor Myo2p propels the movement of most organelles. We recently identified Inp2p as the peroxisome-specific receptor for Myo2p. In this study, we delineate the region of Myo2p devoted to binding peroxisomes. Using mutants of Myo2p specifically impaired in peroxisome binding, we dissect cell cycle–dependent and peroxisome partitioning–dependent mechanisms of Inp2p regulation. We find that although total Inp2p levels oscillate with the cell cycle, Inp2p levels on individual peroxisomes are controlled by peroxisome inheritance, as Inp2p aberrantly accumulates and decorates all peroxisomes in mother cells when peroxisome partitioning is abolished. We also find that Inp2p is a phosphoprotein whose level of phosphorylation is coupled to the cell cycle irrespective of peroxisome positioning in the cell. Our findings demonstrate that both organelle positioning and cell cycle progression control the levels of organelle-specific receptors for molecular motors to ultimately achieve an equidistribution of compartments between mother and daughter cells.

PEX14 is required for microtubule-based peroxisome motility in human cells

“…This is due to the fact that: (1) some peroxins are present in functionally overlapping forms, like the ubiquitin-conjugating enzymes of the peroxisomal protein import machinery (Grou et al, 2008) and (2) other peroxins have different cellular functions in addition to their peroxisome-specific roles and thus, inactivation of the corresponding genes lead to more generalized cellular defects and severe human diseases that are not immediately recognized as PBDs. These processes include peroxisome fission, regulated degradation, inheritance and motility, which require proteins that are also necessary for the maintenance of other organelles (Fagarasanu et al, 2009;Farre et al, 2009;Waterham et al, 2007). Thus, because of the functional redundancy of peroxins and the sharing of peroxins by different organelles, other strategies have to be employed to identify such peroxins with overlapping function.…”

Getting a camel through the eye of a needle: the import of folded proteins by peroxisomes

“…As well as arising from the ER, peroxisomes can proliferate, divide and be partitioned between daughter cells during division (Motley and Hettema, 2007;Fagarasanu et al, 2009). Peroxisomes are dynamic organelles which move on the actin-myosin system in plants (Mathur et al, 2002) and yeast (Fagarasanu et al, 2009), and on microtubules in mammals (Schrader et al, 2000). Consistent with the ability to be derived from the ER membrane, peroxisomes appear to have been an 'invention' of eukaryotic cells (Schluter et al, 2006) and are found in almost all eukaryotes.…”

Sharing the cell's bounty – organelle inheritance in yeast

“…Mutagenesis of conserved surface amino acids in the tail identified patches required for its binding specifically to vacuoles, mitochondria, secretory vesicles and peroxisomes (Altmann et al, 2008;Catlett et al, 2000;Catlett and Weisman, 1998;Fagarasanu et al, 2009;Pashkova et al, 2006). Confirmation that these patches represent bona fide binding sites for organelles was obtained by demonstrating that they are the sites at which the corresponding organelle-specific adaptors bind to Myo2p (Fagarasanu et al, 2009;Ishikawa et al, 2003;Lipatova et al, 2008). Later work showed that binding of eight of the nine known Myo2p cargo adaptors overlaps at one of two distinct Myo2p surface patches (Eves et al, 2012).…”

“…Later work showed that binding of eight of the nine known Myo2p cargo adaptors overlaps at one of two distinct Myo2p surface patches (Eves et al, 2012). This finding has challenged the concept that Myo2p acts as a scaffold that simultaneously exposes sites for attachment to its different cargoes; rather it suggests that different types of organelles compete for access to Myo2p by steric exclusion of other organelles and that the availability of Myo2p adaptors on the surface of organelles has to be tightly regulated to dictate the precise timing of Myo2p recruitment and organelle motility (Fagarasanu et al, 2009 Fig. 1.…”

“…Inp2p and Vac17p fluctuate in level with the cell cycle; they reach maximum levels during peroxisome and vacuole inheritance and are degraded after their organelles have been delivered to the bud (Fagarasanu et al, 2006;Peng and Weisman, 2008). Inp2p and Vac17p each contain several recognition sites for the cyclin-dependent kinase Cdk1p and are phosphorylated during the cell cycle (Fagarasanu et al, 2009;Peng and Weisman, 2008). Direct phosphorylation of Vac17p by Cdk1p has been implicated in the increased affinity of Vac17p for Myo2p (Peng and Weisman, 2008).…”