Filopodia as sensors

• Published in: Cellular signalling 2013-11, Vol.25 (11), p.2298-2311
• Main Authors: Heckman, C.A., Plummer, H.K.
• Format: Article
• Language: English
• Subjects: Actins - chemistry; Actins - metabolism; Animals; Axon pathfinding; Biocompatibility; Calcium - metabolism; Chemotaxis; Chemotaxis - physiology; Classification; Contact inhibition; Cues; Ear; Ear, Inner - cytology; Ear, Inner - physiology; Epididymis - cytology; Epididymis - physiology; Extracellular Matrix - chemistry; Extracellular Matrix - metabolism; Haptotaxis; Humans; Integrins - chemistry; Integrins - metabolism; Ion channels; Male; Mechanoreceptors - cytology; Mechanoreceptors - physiology; Neurite outgrowth; Neurons; Neurons - physiology; Neurons - ultrastructure; Osteocytes - cytology; Osteocytes - physiology; Perturbation; Proteins; Pseudopodia - physiology; Pseudopodia - ultrastructure; Quantitative morphology; Rho-family GTPases; Ruffling; Sensors; Signal Transduction - physiology; Stereocilia - physiology; Stereocilia - ultrastructure
• ISSN: 0898-6568; 1873-3913
• DOI: 10.1016/j.cellsig.2013.07.006

Filopodia are sensors on both excitable and non-excitable cells. The sensing function is well documented in neurons and blood vessels of adult animals and is obvious during dorsal closure in embryonic development. Nerve cells extend neurites in a bidirectional fashion with growth cones at the tips where filopodia are concentrated. Their sensing of environmental cues underpins the axon's ability to “guide,” bypassing non-target cells and moving toward the target to be innervated. This review focuses on the role of filopodia structure and dynamics in the detection of environmental cues, including both the extracellular matrix (ECM) and the surfaces of neighboring cells. Other protrusions including the stereocilia of the inner ear and epididymus, the invertebrate Type I mechanosensors, and the elongated processes connecting osteocytes, share certain principles of organization with the filopodia. Actin bundles, which may be inside or outside of the excitable cell, function to transduce stress from physical perturbations into ion signals. There are different ways of detecting such perturbations. Osteocyte processes contain an actin core and are physically anchored on an extracellular structure by integrins. Some Type I mechanosensors have bridge proteins that anchor microtubules to the membrane, but bundles of actin in accessory cells exert stress on this complex. Hair cells of the inner ear rely on attachments between the actin-based protrusions to activate ion channels, which then transduce signals to afferent neurons. In adherent filopodia, the focal contacts (FCs) integrated with ECM proteins through integrins may regulate integrin-coupled ion channels to achieve signal transduction. Issues that are not understood include the role of Ca2+ influx in filopodia dynamics and how integrins coordinate or gate signals arising from perturbation of channels by environmental cues. •Filopodia react to non-target cells with a touch-and-freeze behavior.•As in sensory dendritic protrusions, the actin bundle serves as a flexion detector.•Proteins with a dual function as enzymes and adaptors are implicated in signaling.•Sensing seems to rely on opening of ion channels caused by mechanical perturbation.•The role of integrin in modulating signal detection and transmission is obscure.