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Rab Cascades

Rab Cascades

Rab GTPases act in a regulated cascade during membrane fusion, helping the lipid bilayers mix. The Rab family of proteins are active when bound to GTP, and inactive when bound to GDP. Hence, they act as guanine nucleotide-dependent molecular switches. Rab-GTP recognizes and binds to long or short-range tethering proteins to capture the target vesicle. These tethers coordinate with SNAREs on the vesicle and the target membrane to assemble the trans SNARE complex that locks the mixing bilayers.

Rab Proteins

Rab Proteins

Rab proteins constitute the largest family of monomeric GTPases, of which 70 members are present in humans. Rab proteins and their effectors regulate consecutive stages of vesicle transport such as vesicle transport, docking, and fusion to the correct recipient membrane.
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...

Microtubules in Signaling

Microtubules in Signaling

The primary cilium, made up of microtubules, acts as antennae on the cell surfaces for relaying external stimuli into the cells. These fine hair-like structures are present, generally one per cell. These are non-motile cilia in a 9+0 microtubules arrangement, where the central pair of microtubules are absent. The primary cilia arise from the basal body embedded in the cell membrane. Intraflagellar transport (IFT) carries requisite proteins from the cytoplasm to the cilium because the primary...

Mechanism of Filopodia Formation

Mechanism of Filopodia Formation

Filopodia are thin, actin-rich cellular protrusions that play an important role in many fundamental cellular functions. They vary in their occurrence, length, and positioning in different cell types, suggesting their diverse roles.
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...

Mechanism of Lamellipodia Formation

Mechanism of Lamellipodia Formation

Cells migrating in response to external stimuli form lamellipodia, which are thin membrane protrusions supported by a mesh of linked, branched, or unbranched actin filaments. These actin filaments interact with myosin motor proteins, creating the dynamic actomyosin complex within the cytoskeleton. Contractility, or the ability to generate contractile stress, is inherent to the actomyosin complex. It helps cells detect the stiffness of the surrounding ECM and exert contractile force for...

Cytoskeletal Coordination in Cell Migration

Cytoskeletal Coordination in Cell Migration

A migrating cell changes its shape during the cyclic events of attachment and detachment from the substratum and repositions the cell organelles correspondingly. These complex events are orchestrated by the dynamic cytoskeletal network comprising actin filaments, intermediate filaments, and microtubules. Cytoskeletal crosstalk — the direct and indirect communication between the different components — is crucial for this coordination. Direct communication involves various linker...

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Related Experiment Video

Updated: Jun 7, 2025

Simple Detection of Primary Cilia by Immunofluorescence

Simple Detection of Primary Cilia by Immunofluorescence

Published on: May 15, 2020

Rab11-Rab8 cascade dynamics in primary cilia and membrane tubules.

Ipsita Saha¹, Christine Insinna¹, Christopher J Westlake¹

¹Laboratory of Cellular and Developmental Signaling, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA.

|November 9, 2024

Summary

The Rab11-Rab8 cascade, involving Rabin8 guanine nucleotide exchange factor (GEF), is crucial for cellular transport. This study clarifies Rab protein dynamics and their role in membrane conversion and ciliary trafficking.

Keywords:

CP: Cell biology Rab cascade Rab membrane loading long tubular membrane membrane conversion primary cilium

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Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells

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Area of Science:

Cell Biology
Molecular Biology
Membrane Trafficking

Background:

The Rab11-Rab8 cascade, regulated by Rabin8 (Rab8 guanine nucleotide exchange factor), is vital for membrane transport.
However, the dynamics of Rab protein loading and exchange on membranes remain poorly understood.

Purpose of the Study:

To investigate the protein dynamics of Rab11, Rab8, and Rabin8 using advanced imaging techniques.
To elucidate the role of the Rab11-Rab8 cascade in ciliary trafficking and association with long tubular membranes (LTMs).

Main Methods:

Fluorescence imaging techniques, including fluorescence loss in photobleaching (FRAP) and super-resolution imaging.
Studies were conducted in human cells and zebrafish embryos.

Main Results:

Rab8 ciliary trafficking necessitates both Rab11 and Rabin8.
Rab11 is recruited to cilia during ciliogenesis in conjunction with Rab8.
The cascade is essential for Rab8 association with LTMs, with Rab11 exchange dynamics dependent on Rabin8 GEF activity.
Cascade-dependent Rab8 loading onto enlarged Rab11-Rabin8 membrane structures was observed.

Conclusions:

The Rab11-Rab8 cascade is integral to membrane conversion processes.
This pathway plays a multifunctional role in cellular trafficking, expanding current knowledge.