Apoptosis

Quantitation of mitochondrial dynamics by photolabeling of individual organelles shows that mitochondrial fusion is blocked during the Bax activation phase of apoptosis. Karbowski, M. et al. J. Cell Biol. 9 Feb 2004 (doi:10.1083/jcb.200309082)

A delicate balance between fusion and fission regulates the size, shape and number of mitochondria, but when this balance is altered in favour of fission, apoptosis occurs. Karbowski and colleagues describe a new technique — that uses a photoactivatable green fluorescent protein targeted to the mitochondrial matrix — to measure mitochondrial dynamics in vivo. Using this method, the authors show that mitochondrial fusion is blocked during apoptosis, and this blockage could be caused by the activation of Bax or Bak.

Signal Transduction

APPL proteins link Rab5 to nuclear signal transduction via an endosomal compartment. Miaczynska, M. et al. Cell 116, 445–456 (2004)

Miaczynska et al. have discovered a new signalling pathway that directly links the small GTPase Rab5, a regulator of endocytosis, with intracellular signalling. The pathway involves two Rab5 effectors, APPL1 and APPL2, which are concentrated in the endosomes. In response to external stimuli, APPL1 translocates to the nucleus and interacts with the NuRD/MeCP1 complex, which regulates gene expression. This work provides further evidence that endosomes aren't merely required for downregulating activated cell-surface receptors — they are also important for intracellular signalling.

Cell Adhesion

Localized stabilization of microtubules by integrin- and FAK-facilitated Rho signaling. Palazzo, A. F. et al. Science 303, 836–839 (2004) Integrins regulate Rac targeting by internalization of membrane domains. del Pozo, M. A. et al. Science 303, 839–842 (2004)

Integrin signalling regulates numerous cellular processes, including cell adhesion and migration, and is mediated by Rho GTPases, such as Rho and Rac. Two studies now show that integrins use lipid rafts to target Rho and Rac to the plasma membrane and couple them to downstream effectors of the integrin-signalling pathway. del Pozo et al. found that Rac associates preferentially with lipid rafts, and the internalization of lipid rafts after cell detachment causes the loss of Rac membrane targeting and integrin signalling. Palazzo et al. report that the localized microtubule stabilization at the leading edge of migrating cells is mediated by integrin signalling, which regulates the local coupling of Rho to its effector Diaphanous (Dia) by the localization of lipid rafts at the leading edge. These findings implicate lipid rafts as spatial regulators in signalling events.