Abstract
The current view of peroxisome inheritance provides for the formation of new peroxisomes by both budding from the endoplasmic reticulum and autonomous division. Here we investigate peroxisome-cytoskeleton interactions and show by proteomics, biochemical and immunofluorescence analyses that actin, non-muscle myosin IIA (NMM IIA), RhoA, Rho kinase II (ROCKII) and Rab8 associate with peroxisomes. Our data provide evidence that (i) RhoA in its inactive state, maintained for example by C. botulinum toxin exoenzyme C3, dissociates from peroxisomes enabling microtubule-based peroxisomal movements and (ii) dominant-active RhoA targets to peroxisomes, uncouples the organelles from microtubules and favors Rho kinase recruitment to peroxisomes. We suggest that ROCKII activates NMM IIA mediating local peroxisomal constrictions. Although our understanding of peroxisome-cytoskeleton interactions is still incomplete, a picture is emerging demonstrating alternate RhoA-dependent association of peroxisomes to the microtubular and actin cytoskeleton. Whereas association of peroxisomes to microtubules clearly serves bidirectional, long-range saltatory movements, peroxisome-acto-myosin interactions may support biogenetic functions balancing peroxisome size, shape, number, and clustering.
Highlights
Mammalian peroxisomes associate with the microtubular cytoskeleton for intracellular transport [1,2]
We demonstrated that peroxisome motility is subject to regulation by extracellular ATP-lysophosphatidic acid (LPA) receptor co-stimulation
RhoA signaling regulates peroxisome motility Our current view of the multiple signaling pathways regulating peroxisome microtubule interaction encompasses both activation of PLA2 via Gi/Go liberating arachidonic acid by ATP and RhoA via G12/13 by extracellular LPA [3,4,31]
Summary
Mammalian peroxisomes associate with the microtubular cytoskeleton for intracellular transport [1,2]. Via G12/13 the LPA receptor activates the Rho pathway preventing long-range peroxisomal motility that seems to be regulated by a complex signaling network [4,6]. These studies did not show the involvement of the actin cytoskeleton in the motility of mammalian peroxisomes. One is based on actin polymerization itself propelling organelles by an ‘‘actin comet tail’’ toward the cell center. This type has been described for phagosomes and macropinosomes and may be involved in transport between endosomes and lysosomes [12,13]. This myosin-dependent movement has been implicated in dynamics of the ER, lysosomes, Golgi-derived vesicles, secretory granules, recycling endosomes and melanosomes [14,15,16]
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