Specific Interaction with Cardiolipin Triggers Functional Activation of Dynamin-Related Protein 1

Dynamin-Related Protein 1 (Drp1), a large GTPase of the dynamin superfamily, is required for mitochondrial fission in healthy and apoptotic cells. Drp1 activation is a complex process that involves translocation from the cytosol to the mitochondrial outer membrane (MOM) and assembly into rings/spirals at the MOM, leading to membrane constriction/division. Similar to dynamins, Drp1 contains GTPase (G), bundle signaling element (BSE) and stalk domains. However, instead of the lipid-interacting Pleckstrin Homology (PH) domain present in the dynamins, Drp1 contains the so-called B insert or variable domain that has been suggested to play an important role in Drp1 regulation. Different proteins have been implicated in Drp1 recruitment to the MOM, although how MOM-localized Drp1 acquires its fully functional status remains poorly understood. We found that Drp1 can interact with pure lipid bilayers enriched in the mitochondrion-specific phospholipid cardiolipin (CL). Building on our previous study, we now explore the specificity and functional consequences of this interaction. We show that a four lysine module located within the B insert of Drp1 interacts preferentially with CL over other anionic lipids. This interaction dramatically enhances Drp1 oligomerization and assembly-stimulated GTP hydrolysis. Our results add significantly to a growing body of evidence indicating that CL is an important regulator of many essential mitochondrial functions.

Density-potential mapping in the standard and quantum electrodynamical time-dependent density functional theory

131 p.

Interaction between the 5-HT system and the basal ganglia: functional implication and therapeutic perspective in Parkinson's disease

The neurotransmitter serotonin (5-HT) has a multifaceted function in the modulation of information processing through the activation of multiple receptor families, including G-protein-coupled receptor subtypes (5-HT1, 5-HT2, 5-HT4-7) and ligand-gated ion channels (5-HT3). The largest population of serotonergic neurons is located in the midbrain, specifically in the raphe nuclei. Although the medial and dorsal raphe nucleus (DRN) share common projecting areas, in the basal ganglia (BG) nuclei serotonergic innervations come mainly from the DRN. The BG are a highly organized network of subcortical nuclei composed of the striatum (caudate and putamen), subthalamic nucleus (STN), internal and external globus pallidus (or entopeduncular nucleus in rodents, GPi/EP and GPe) and substantia nigra (pars compacta, SNc, and pars reticulata, SNr). The BG are part of the cortico-BG-thalamic circuits, which play a role in many functions like motor control, emotion, and cognition and are critically involved in diseases such as Parkinson's disease (PD). This review provides an overview of serotonergic modulation of the BG at the functional level and a discussion of how this interaction may be relevant to treating PD and the motor complications induced by chronic treatment with L-DOPA.

Approximate Solutions by Truncated Taylor Series Expansions of Nonlinear Differential Equations and Related Shadowing Property with Applications

This paper investigates the errors of the solutions as well as the shadowing property of a class of nonlinear differential equations which possess unique solutions on a certain interval for any admissible initial condition. The class of differential equations is assumed to be approximated by well-posed truncated Taylor series expansions up to a certain order obtained about certain, in general nonperiodic, sampling points t(i) is an element of [t(0), t(J)] for i = 0, 1, . . . , J of the solution. Two examples are provided.

Validation of back-calculation equations for juvenile bluefish (Pomatomus saltatrix) with the use of tetracycline-marked otoliths

In recent years, a decrease in the abundance of bluefish (Pomatomus saltatrix) has been observed (Fahay et al., 1999; Munch and Conover, 2000) that has led to increased interest in a better understanding the life history of the species. Estimates of several young-of-the-year (YOY) life history characteristics, including the importance and use of estuaries as nursery habitat (Kendall and Walford, 1979) and size-dependant mortality (Hare and Cowen, 1997), are reliant upon the accuracy of growth determination. By using otoliths, it is possible to use back-calculation formulae (BCFs) to estimate the length at certain ages and stages of development for many species of fishes. Use of otoliths to estimate growth in this way can provide the same information as long-term laboratory experiments and tagging studies without the time and expense of rearing or recapturing fish. The difficulty in using otoliths in this way lies in validating that 1) there is constancy in the periodicity of the increment formation, and 2) there is no uncoupling of the relationship between somatic and otolith growth. To date there are no validation studies demonstrating the relationship between otolith growth and somatic growth for bluefish. Daily increment formation in otoliths has been documented for larval (Hare and Cowen, 1994) and juvenile bluefish (Nyman and Conover, 1988). Hare and Cowen (1995) found ageindependent variability in the ratio of otolith size to body length in early age bluefish, although these differences varied between ontogenetic stages. Furthermore, there have been no studies where an evaluation of back-calculation methods has been combined with a validation of otolithderived lengths for juvenile bluefish.