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The large family of Rab GTPases has various functions, including the assembly of proteins required for endocytosis and membrane trafficking. Now, a new function for a Rab is emerging. On page 659, Alto et al. describe a Rab that affects mitochondrial fission. This GTPase, Rab32, also has an unusual binding partner, the cAMP-dependent kinase PKA.
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8 u: s- h4 V; Q) t* Y5 `The authors originally sought to identify novel AKAPs, proteins that anchor PKA to subcellular domains. They found Rab32, the first Ras family member GTPase shown to interact directly with PKA. Although a functional connection between the two has yet to be shown, association of the enzymes may facilitate localization of signal transduction pathways. The group is currently addressing this possibility by looking for other proteins that may interact with the complex.. _) k% |! j* A, f' @4 K
8 u( p/ l5 N5 H) ?9 o" nAfter confirming that Rab32 was an AKAP, Alto et al. were surprised to find that it localized to mitochondria, where PKA is known to phosphorylate several proteins, including those involved in apoptotic pathways. Rab32's function there seems to be separate from its PKA-binding activity, however, as mitochondria were not affected by Rab32 mutations that abolished this binding. In contrast, overexpression of a dominant–negative version of Rab32 lacking its GTP-binding activity resulted in an aggregation of elongated mitochondria around the microtubule organizing center. Thus, Rab32 activity may be required for mitochondrial fission. This suggests that Rab32 function is similar to that of other Rab proteins in trafficking, where they help assemble complexes required for fusion and fission.(Aggregates of large mitochondria (red) f) |
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发表于 2009-3-6 00:14
发表于 2015-5-24 18:00
