The cytoskeletal polymers--actin, microtubules, and intermediate filaments--are interlinked by coordinated protein interactions to form a complex three-dimensional cytoskeletal network. Association of actin filaments with microtubules is important for various cellular processes such as cell division, migration, vesicle and organelle transport, and axonal growth. Several proteins including signaling molecules, motor proteins, and proteins directly or indirectly associated with microtubules and actin are involved in bridging the cytoskeletal components. Microtubule-associated proteins (MAPs) belonging to the MAP1, 2, 4 family and Tau proteins have been identified as key players that directly crosslink the two cytoskeletons. This review summarizes the current understanding of the interactions of these MAPs with actin filaments and their role in forming the actin-microtubule network and further discusses how the in vitro reconstitution assays can be used to study the dynamics of coordinated networks. Understanding the mechanisms by which actin and microtubules interact is key to decipher cancer, wound healing, and neuronal regeneration.

ABSTRACT:We studied the long-term effects of streptozotocin-induced diabetes on tissue-specific cytochrome P450 (CYP) and glutathione-dependent (GSHdependent) xenobiotic metabolism in rats. In addition, we also studied the effect of antidiabetic Momordica charantia (karela) fruit-extract feeding on the modulation of xenobiotic metabolism and oxidative stress in rats with diabetes. Our results have indicated an increase (35-50%) in CYP4A-dependent lauric acid hydroxylation in liver, kidney, and brain of diabetic rats. About a two-fold increase in CYP2E-dependent hepatic aniline hydroxylation and a 90-100% increase in CYP1A-dependent ethoxycoumarin-O-deethylase activities in kidney and brain were also observed. A significant increase (80%) in aminopyrene N-demethylase activity was observed only in rat kidney, and a decrease was observed in the liver and brain of diabetic rats. A significant increase (77%) in NADPH-dependent lipid peroxidation (LPO) in kidney of diabetic rats was also observed. On the other hand, a decrease in hepatic LPO was seen during chronic diabetes. During diabetes an increased expression of CYP1A1, CYP2E1, and CYP4A1 isoenzymes was also seen by Western blot analysis. Karela-juice feeding modulates the enzyme expression and catalytic activities in a tissue-and isoenzyme-specific manner. A marked decrease (65%) in hepatic GSH content and glutathione S-transferase (GST) activity and an increase (about two-fold) in brain GSH and GST activity was observed in diabetic rats. On the other hand, renal GST was markedly reduced, and GSH content was moderately higher than that of control rats. Western blot analyses using specific antibodies have confirmed the tissue- specific alterations in the expression of GST isoenzymes. Karela-juice feeding, in general, reversed the effect of chronic diabetes on the modulation of both P450-dependent monooxygenase activities and GSHdependent oxidative stress related LPO and GST activities. These results have suggested that the modulation of xenobiotic metabolism and oxidative stress in various tissues may be related to altered metabolism of endogenous substrates and hormonal status during diabetes. The findings may have significant implications in elucidating the therapeutic use of antidiabetic drugs and management of Type 1 diabetes in chronic diabetic patients.

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