HIGHLIGHTS from MBoC

In their paper in the January 1, 2016, issue of MBoC, Lawrimore et al. describe the application of ChromoShake, a three-dimensional simulator designed to find the thermodynamically favored states for given chromosome geometries, to a geometric model based on experimentally determined characteristics of the budding yeast centromere (Mol. Biol. Cell 27, 153–166). In the model shown here, the spindle pole bodies (red disks) and kinetochore microtubules (green rods) depict a metaphase configuration. The colored strands represent the centromere regions of the 16 chromosomes. The centromere chromatin is shown under conditions of thermal fluctuation. Chromosome arms extend perpendicular to the spindle axis. Cohesin (white rings) is radially displaced from the spindle axis. (Image: Josh Lawrimore, Joseph K. Aicher, Patrick Hahn, Alyona Fulp, Ben Kompa, Leandra Vicci, Michael Falvo, Russell M. Taylor II, and Kerry Bloom, University of North Carolina at Chapel Hill)

Regulation of Chlamydomonas flagella and ependymal cell motile cilia by ceramide-mediated translocation of GSK3
Ji Na Kong, K. Hardin, M. Dinkins, Guanghu Wang, Qian He, T. Mujadzic, Gu Zhu, J. Bielawski,
S. Spassieva, and E. Bieberich
Cilia are important organelles formed by cell membrane protrusions; however, little is known about their regulation by membrane lipids. A novel, evolutionarily conserved activation mechanism for GSK3 by the sphingolipid (phyto)ceramide is characterized that is critical for ciliogenesis in Chlamydomonas and murine ependymal cells.
Mol. Biol. Cell 26 (24), 4451–4465

Peptide TFP5/TP5 derived from Cdk5 activator P35 provides neuroprotection in the MPTP model of Parkinson’s disease
BK. Binukumar, V. Shukla, N. D. Amin, P. Grant, M. Bhaskar, S. Skuntz, J. Steiner, and H. C. Pant
TFP5/TP5 rescues dopaminergic neurodegeneration induced by MPTP in a mouse model of Parkinson’s disease (PD). The neuroprotective effect of TFP5/TP5 peptide is also associated with marked reduction in neuroinflammation and apoptosis. Selective inhibition of Cdk5/p25 by TFP5/TP5 peptide identifies the kinase as a potential target to reduce neurodegeneration in PD.
Mol. Biol. Cell 26 (24), 4478–4491

CARMIL2 is a novel molecular connection between vimentin and actin essential for cell migration and invadopodia formation
M. H. Lanier, T. Kim, and J. A. Cooper
CARMIL2 is a novel and direct molecular connection between vimentin filaments and actin assembly during cell migration and invadopodia formation. Through two distinct domains, CARMIL2 localizes to vimentin filaments and regulates actin assembly. The biochemical activities of both domains are necessary for cell migration and invasion.
Mol. Biol. Cell 26 (25), 4577–4588

Cell type–dependent mechanisms for formin-mediated assembly of filopodia
L. E. Young, E. G. Heimsath, and H. N. Higgs
Several mammalian formins participate in filopodial assembly, but the identity of the actin nucleation factor is not clear. Nucleation factor requirements differ between nonadherent and adherent cells. Arp2/3 complex is essential in suspension cells, whereas the situation is more complex in adherent cells.
Mol. Biol. Cell 26 (25), 4646–4659

Phosphatidylserine translocation at the yeast trans-Golgi network regulates protein sorting into exocytic vesicles
H. M. Hankins, Y. Y. Sere, N. S. Diab, A. K. Menon, and T. R. Graham
Protein sorting into exocytic vesicles at the yeast trans-Golgi network is believed to be mediated by their coalescence with specific lipids, but how this event is regulated is poorly understood. It is shown that phosphatidylserine flip by Drs2 is required for efficient sorting of the plasma membrane proteins Pma1 and Can1 into exocytic vesicles.
Mol. Biol. Cell 26 (25), 4674–4685

Lamin B1 protein is required for dendrite development in primary mouse cortical neurons
C. Giacomini, S. Mahajani, R. Ruffilli, R. Marotta, and L. Gasparini
Lamin B1 depletion has detrimental effects on brain development. Lamin B1 loss of function affects neuronal development in primary mouse cortical neurons, strongly impairing dendrite length and complexity. This defective dendrite development stems from impaired nuclear ERK signaling and, possibly, mislocalization of nuclear pores.
Mol. Biol. Cell 27 (1), 35–47

Ccdc11 is a novel centriolar satellite protein essential for ciliogenesis and establishment of left–right asymmetry
E. Silva, E. Betleja, E. John, P. Spear, J. J. Moresco, Siwei Zhang, J. R. Yates, III, B. J. Mitchell,
and M. R. Mahjoub
Mutations in CCDC11 cause aberrant placement of internal organs and congenital heart disease in humans. Ccdc11 is a novel component of centriolar satellites and plays a critical role in motile and sensory ciliogenesis. The results implicate centriolar satellites in the pathology of left–right patterning and heart disease.
Mol. Biol. Cell 27 (1), 48–63

A complex of Rab13 with MICAL-L2 and α-actinin-4 is essential for insulin-dependent GLUT4 exocytosis
Yi Sun, J. Jaldin-Fincati, Zhi Liu, P. J. Bilan, and A. Klip
Rab13 is necessary for insulin-regulated GLUT4-vesicle exocytosis in muscle. Biochemical and imaging analyses provide evidence that activated Rab13 engages a scaffold protein MICAL-L2 to form a complex with Rab13 and α-actinin-4. Through GLUT4 interaction with α-actinin-4, GLUT4 vesicles are recruited to the muscle plasma membrane.
Mol. Biol. Cell 27 (1), 75–89

ChromoShake: a chromosome dynamics simulator reveals that chromatin loops stiffen centromeric chromatin
J. Lawrimore, J. K. Aicher, P. Hahn, A. Fulp, B. Kompa, L. Vicci, M. Falvo, R. M. Taylor, II, and K. Bloom
A novel chromosome simulator recapitulates the position and dynamics of centromeric chromatin in a model composed of cross-linked intramolecular loops. Simulations reveal that chromatin loops stiffen the centromere and dictate the distribution of pericentric cohesin.
Mol. Biol. Cell 27 (1), 153–166

Locus-specific gene repositioning in prostate cancer
M. Leshner, M. Devine, G. W. Roloff, L. D. True, T. Misteli, and K. J. Meaburn
The spatial organization of the genome is altered in prostate cancer compared to normal tissue in a gene-specific manner. The repositioning of two genes, FLI1 and MMP9, is specific to cancer, and the positioning patterns of these genes may serve as diagnostic biomarkers.
Mol. Biol. Cell 27 (2), 236–246