EB-SUN, a new microtubule plus-end tracking protein in .

Microtubule (MT) regulation is essential for oocyte development. In , MT stability, polarity, abundance, and orientation undergo dynamic changes across developmental stages. In our effort to identify novel microtubule-associated proteins that regulate MTs in the ovary, we identified a previously uncharacterized gene, CG18190, which encodes a novel MT end-binding (EB) protein, which we propose to name EB-SUN.

"Mitotic" kinesin-5 is a dynamic brake for axonal growth.

During neuronal development, neurons undergo significant microtubule reorganization to shape axons and dendrites, establishing the framework for efficient wiring of the nervous system. Previous studies from our laboratory demonstrated the key role of kinesin-1 in driving microtubule-microtubule sliding, which provides the mechanical forces necessary for early axon outgrowth and regeneration in In this study, we reveal the critical role of kinesin-5, a mitotic motor, in modulating the development of postmitotic neurons. Kinesin-5, a conserved homotetrameric motor, typically functions in mitosis by sliding antiparallel microtubules apart in the spindle.

EB-SUN, a New Microtubule Plus-End Tracking Protein in .

Microtubule (MT) regulation is essential for oocyte development. In , MT stability, polarity, abundance, and orientation undergo dynamic changes across developmental stages. In our effort to identify novel microtubule-associated proteins (MAPs) that regulate MTs in the ovary, we identified a previously uncharacterized gene, CG18190, encoding a novel MT end-binding (EB) protein, which we propose to name EB-SUN.

Tubulin CFEOM mutations both inhibit or activate kinesin motor activity.

Kinesin-mediated transport along microtubules is critical for axon development and health. Mutations in the kinesin Kif21a, or the microtubule subunit β-tubulin, inhibit axon growth and/or maintenance resulting in the eye-movement disorder congenital fibrosis of the extraocular muscles (CFEOM). While most examined CFEOM-causing β-tubulin mutations inhibit kinesin-microtubule interactions, Kif21a mutations activate the motor protein.

The dynamic duo of microtubule polymerase Mini spindles/XMAP215 and cytoplasmic dynein is essential for maintaining oocyte fate.

In many species, only one oocyte is specified among a group of interconnected germline sister cells. In , 16 interconnected cells form a germline cyst, where one cell differentiates into an oocyte, while the rest become nurse cells that supply the oocyte with mRNAs, proteins, and organelles through intercellular cytoplasmic bridges named ring canals via microtubule-based transport. In this study, we find that a microtubule polymerase Mini spindles (Msps), the homolog of XMAP215, is essential for maintenance of the oocyte specification.

Nanoscale architect: Illuminating the key organizer of the fruit fly's sensory world.

Mechanosensory neurons utilize specialized compartments called mechanosensory organelles (MOs) to process external forces, yet the MO organization mechanisms remained unclear. In this issue, Song et al. (2023.

Self-organized intracellular twisters.

Life in complex systems, such as cities and organisms, comes to a standstill when global coordination of mass, energy, and information flows is disrupted. Global coordination is no less important in single cells, especially in large oocytes and newly formed embryos, which commonly use fast fluid flows for dynamic reorganization of their cytoplasm. Here, we combine theory, computing, and imaging to investigate such flows in the Drosophila oocyte, where streaming has been proposed to spontaneously arise from hydrodynamic interactions among cortically anchored microtubules loaded with cargo-carrying molecular motors.

Self-organized intracellular twisters.

Life in complex systems, such as cities and organisms, comes to a standstill when global coordination of mass, energy, and information flows is disrupted. Global coordination is no less important in single cells, especially in large oocytes and newly formed embryos, which commonly use fast fluid flows for dynamic reorganization of their cytoplasm. Here, we combine theory, computing, and imaging to investigate such flows in the Drosophila oocyte, where streaming has been proposed to spontaneously arise from hydrodynamic interactions among cortically anchored microtubules loaded with cargo-carrying molecular motors.

Gigaxonin is required for intermediate filament transport.

Gigaxonin is an adaptor protein for E3 ubiquitin ligase substrates. It is necessary for ubiquitination and degradation of intermediate filament (IF) proteins. Giant axonal neuropathy is a pathological condition caused by mutations in the GAN gene that encodes gigaxonin.

oocyte specification is maintained by the dynamic duo of microtubule polymerase Mini spindles/XMAP215 and dynein.

Unlabelled: In many species, only one oocyte is specified among a group of interconnected germline sister cells. In , 16-cell interconnected cells form a germline cyst, where one cell differentiates into an oocyte, while the rest become nurse cells that supply the oocyte with mRNAs, proteins, and organelles through intercellular cytoplasmic bridges named ring canals via microtubule-based transport. In this study, we find that a microtubule polymerase Mini spindles (Msps), the homolog of XMAP215, is essential for the oocyte fate determination.

Go with the flow - bulk transport by molecular motors.

Cells are the smallest building blocks of all living eukaryotic organisms, usually ranging from a couple of micrometers (for example, platelets) to hundreds of micrometers (for example, neurons and oocytes) in size. In eukaryotic cells that are more than 100 µm in diameter, very often a self-organized large-scale movement of cytoplasmic contents, known as cytoplasmic streaming, occurs to compensate for the physical constraints of large cells. In this Review, we discuss cytoplasmic streaming in multiple cell types and the mechanisms driving this event.

Tissue architecture: Two kinesins collaborate in building basement membrane.

Basement membranes are essential for tissue architecture and development. A new study reveals that two microtubule motors, kinesin-3 and kinesin-1, work collaboratively to direct basement membrane protein secretion in the Drosophila follicular epithelium for correct tissue movement.

A novel mechanism of bulk cytoplasmic transport by cortical dynein in ovary.

Cytoplasmic dynein, a major minus-end directed microtubule motor, plays essential roles in eukaryotic cells. oocyte growth is mainly dependent on the contribution of cytoplasmic contents from the interconnected sister cells, nurse cells. We have previously shown that cytoplasmic dynein is required for oocyte growth and assumed that it simply transports cargoes along microtubule tracks from nurse cells to the oocyte.

Ataxin-2 is essential for cytoskeletal dynamics and neurodevelopment in .

Ataxin-2 (Atx2) is a highly conserved RNA binding protein. Atx2 undergoes polyglutamine expansion leading to amyotrophic lateral sclerosis (ALS) or spinocerebellar ataxia type 2 (SCA2). However, the physiological functions of Atx2 in neurons remain unknown.

Gatekeeper function for Short stop at the ring canals of the Drosophila ovary.

Growth of the Drosophila oocyte requires transport of cytoplasmic materials from the interconnected sister cells (nurse cells) through ring canals, the cytoplasmic bridges that remained open after incomplete germ cell division. Given the open nature of the ring canals, it is unclear how the direction of transport through the ring canal is controlled. In this work, we show that a single Drosophila spectraplakin Short stop (Shot) controls the direction of flow from nurse cells to the oocyte.

Kinetochore protein Spindly controls microtubule polarity in axons.

Microtubule polarity in axons and dendrites defines the direction of intracellular transport in neurons. Axons contain arrays of uniformly polarized microtubules with plus-ends facing the tips of the processes (plus-end-out), while dendrites contain microtubules with a minus-end-out orientation. It has been shown that cytoplasmic dynein, targeted to cortical actin, removes minus-end-out microtubules from axons.

Competition between kinesin-1 and myosin-V defines posterior determination.

Local accumulation of ) mRNA in the oocyte determines the posterior pole of the future embryo. Two major cytoskeletal components, microtubules and actin filaments, together with a microtubule motor, kinesin-1, and an actin motor, myosin-V, are essential for mRNA posterior localization. In this study, we use Staufen, an RNA-binding protein that colocalizes with mRNA, as a proxy for mRNA.

Ser/Thr kinase Trc controls neurite outgrowth in by modulating microtubule-microtubule sliding.

Correct neuronal development requires tailored neurite outgrowth. Neurite outgrowth is driven in part by microtubule-sliding - the transport of microtubules along each other. We have recently demonstrated that a 'mitotic' kinesin-6 (Pavarotti in ) effectively inhibits microtubule-sliding and neurite outgrowth.

Unconventional Roles of Cytoskeletal Mitotic Machinery in Neurodevelopment.

At first look, cell division and neurite formation seem to be two different, essential biological processes. However, both processes require extensive reorganization of the cytoskeleton, and especially microtubules. Remarkably, in recent years, independent work from several groups has shown that multiple cytoskeletal components previously considered specific for the mitotic machinery play important roles in neurite initiation and extension.

Conserved role for Ataxin-2 in mediating endoplasmic reticulum dynamics.

Ataxin-2, a conserved RNA-binding protein, is implicated in the late-onset neurodegenerative disease Spinocerebellar ataxia type-2 (SCA2). SCA2 is characterized by shrunken dendritic arbors and torpedo-like axons within the Purkinje neurons of the cerebellum. Torpedo-like axons have been described to contain displaced endoplasmic reticulum (ER) in the periphery of the cell; however, the role of Ataxin-2 in mediating ER function in SCA2 is unclear.

Repurposing Kinetochore Microtubule Attachment Machinery in Neurodevelopment.

Kinetochore-microtubule attachments are essential to direct proper chromosome segregation during cell division. In this issue of Developmental Cell, Cheerambathur et al. (2019) and Zhao et al.

Microtubule Dynamics, Kinesin-1 Sliding, and Dynein Action Drive Growth of Cell Processes.

Recent experimental studies of the role of microtubule sliding in neurite outgrowth suggested a qualitative model, according to which kinesin-1 motors push the minus-end-out microtubules against the cell membrane and generate the early cell processes. At the later stage, dynein takes over the sliding, expels the minus-end-out microtubules from the neurites, and pulls in the plus-end-out microtubules that continue to elongate the nascent axon. This model leaves unanswered a number of questions: why is dynein unable to generate the processes alone, whereas kinesin-1 can? What is the role of microtubule dynamics in process initiation and growth? Can the model correctly predict the rates of process growth in control and dynein-inhibited cases? What triggers the transition from kinesin-driven to dynein-driven sliding? To answer these questions, we combine computational modeling of a network of elastic dynamic microtubules and kinesin-1 and dynein motors with measurements of the process growth kinetics and pharmacological perturbations in Drosophila S2 cells.

Ooplasmic flow cooperates with transport and anchorage in oocyte posterior determination.

The posterior determination of the embryo is defined by the posterior localization of ) mRNA in the oocyte. Defects of its localization result in a lack of germ cells and failure of abdomen specification. A microtubule motor kinesin-1 is essential for mRNA posterior localization.

Kinesin-dependent transport of keratin filaments: a unified mechanism for intermediate filament transport.

Keratin intermediate filaments (IFs) are the major cytoskeletal component in epithelial cells. The dynamics of keratin IFs have been described to depend mostly on the actin cytoskeleton, but the rapid transport of fully polymerized keratin filaments has not been reported. In this work, we used a combination of photoconversion experiments and clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeats-associated protein 9 genome editing to study the role of microtubules and microtubule motors in keratin filament transport.