There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.

Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

I and i

Microtubules have fundamental roles in many essential biological processes, including cell division and intracellular transport. They assemble and disassemble from their two ends, denoted the plus end and the minus end. Significant advances have been made in our understanding of microtubule plus-end-tracking proteins (+TIPs) such as end-binding protein 1 (EB1), XMAP215, selected kinesins and dynein. By contrast, information on microtubule minus-end-targeting proteins (-TIPs), such as the calmodulin-regulated spectrin-associated proteins (CAMSAPs) and Patronin, has only recently started to emerge. Here, we review our current knowledge of factors, including microtubule-targeting agents, that associate with microtubule ends to control the dynamics and function of microtubules during the cell cycle and development.

Control of microtubule organization and dynamics: two ends in the limelight

This review discusses one-dimensional supramolecular polymers that form in aqueous media. First, naturally occurring supramolecular polymers are described, in particular, amyloid fibrils, actin filaments, and microtubules. Their structural, thermodynamic, kinetic, and nanomechanical properties are highlighted, as well as their importance for the advancement of biologically inspired supramolecular polymer materials. Second, five classes of synthetic supramolecular polymers are described: systems based on (1) hydrogen-bond motifs, (2) large π-conjugated surfaces, (3) host–guest interactions, (4) peptides, and (5) DNA. We focus on recent studies that address key challenges in the field, providing mechanistic understanding, rational polymer design, important functionality, robustness, or unusual thermodynamic and kinetic properties.

Supramolecular Polymers in Aqueous Media

Building the Neuronal Microtubule Cytoskeleton

Endocytosis occurs at the cell surface and involves internalization of the plasma membrane (PM) along with its constituent membrane proteins and lipids. Endocytosis is involved in sampling of the extracellular milieu and also serves to regulate various processes initiated at the cell surface. These include nutrient uptake, signaling from cell-surface receptors, and many other processes essential for cell and tissue functioning in metazoans. It is also central to the maintenance of PM lipid and protein homeostasis. There are multiple means of internalization that operate concurrently, at the cell surface. With advancement in high-resolution visualization techniques, it is now possible to track multiple endocytic cargo at the same time, revealing a remarkable diversity of endocytic processes in a single cell. A combination of live cell imaging and efficient genetic manipulations has also aided in understanding the functional hierarchy of molecular players in these mechanisms of internalization. Here we provide an account of various endocytic routes, their mechanisms of operation and occurrence across phyla.

/pdf/endocytosis-unplugged-multiple-ways-to-enter-the-cell-4da1m9g4te.pdf

Endocytosis unplugged: multiple ways to enter the cell

Insights into antiparallel microtubule crosslinking by PRC1, a conserved nonmotor microtubule binding protein.

Mammalian Hedgehog (Hh) signal transduction requires a primary cilium, a microtubule-based organelle, and the Gli-Sufu complexes that mediate Hh signalling, which are enriched at cilia tips. Kif7, a kinesin-4 family protein, is a conserved regulator of the Hh signalling pathway and a human ciliopathy protein. Here we show that Kif7 localizes to the cilium tip, the site of microtubule plus ends, where it limits cilium length and controls cilium structure. Purified recombinant Kif7 binds the plus ends of growing microtubules in vitro, where it reduces the rate of microtubule growth and increases the frequency of microtubule catastrophe. Kif7 is not required for normal intraflagellar transport or for trafficking of Hh pathway proteins into cilia. Instead, a central function of Kif7 in the mammalian Hh pathway is to control cilium architecture and to create a single cilium tip compartment, where Gli-Sufu activity can be correctly regulated.

The kinesin-4 protein Kif7 regulates mammalian Hedgehog signalling by organizing the cilium tip compartment

https://www.cell.com/cell/pdf/S0092-8674(13)00760-5.pdf

Marking and Measuring Single Microtubules by PRC1 and Kinesin-4

https://www.cell.com/developmental-cell/pdf/S1534-5807(12)00474-1.pdf

Building Complexity: Insights into Self-Organized Assembly of Microtubule-Based Architectures

Motor and non-motor crosslinking proteins play critical roles in determining the size and stability of microtubule-based architectures. Currently, we have a limited understanding of how geometrical properties of microtubule arrays, in turn, regulate the output of crosslinking proteins. Here we investigate this problem in the context of microtubule sliding by two interacting proteins: the non-motor crosslinker PRC1 and the kinesin Kif4A. The collective activity of PRC1 and Kif4A also results in their accumulation at microtubule plus-ends (‘end-tag’). Sliding stalls when the end-tags on antiparallel microtubules collide, forming a stable overlap. Interestingly, we find that structural properties of the initial array regulate microtubule organization by PRC1-Kif4A. First, sliding velocity scales with initial microtubule-overlap length. Second, the width of the final overlap scales with microtubule lengths. Our analyses reveal how micron-scale geometrical features of antiparallel microtubules can regulate the activity of nanometer-sized proteins to define the structure and mechanics of microtubule-based architectures.

Radhika Subramanian

Papers

Insights into antiparallel microtubule crosslinking by PRC1, a conserved nonmotor microtubule binding protein.

The kinesin-4 protein Kif7 regulates mammalian Hedgehog signalling by organizing the cilium tip compartment

Marking and Measuring Single Microtubules by PRC1 and Kinesin-4

Building Complexity: Insights into Self-Organized Assembly of Microtubule-Based Architectures

Geometry of antiparallel microtubule bundles regulates relative sliding and stalling by PRC1 and Kif4A