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Jarsch, I. K.

Publications and source records attributed to Jarsch, I. K..

2 recordsLinked to original sources

A direct role for SNX9 in the biogenesis of filopodia

Filopodia are finger-like actin-rich protrusions that extend from the cell surface and are important for cell-cell communication and pathogen internalization. The small size and transient nature of filopodia combined with shared usage of actin regulators within cells confounds attempts to identify filopodial proteins. Here, we used phage display phenotypic screening to isolate antibodies that alter the actin morphology of filopodia-like structures in vitro. We found that all of the antibodies that cause shorter FLS interact with SNX9, an actin regulator that binds phosphoinositides during endocytosis and in invadopodia. In cells, we discover SNX9 at specialised filopodia in Xenopus development and that SNX9 is an endogenous component of filopodia that are hijacked by Chlamydia entry. We show the use of antibody technology to identify proteins used in filopodia-like structures, and a role for SNX9 in filopodia.

cell biology

Constrained actin dynamics emerges from variable compositions of actin regulatory protein complexes

Assemblies of actin and its regulators underlie the dynamic morphology of all eukaryotic cells. To begin to understand how diverse regulatory proteins work together to generate actin-rich structures we tracked the assembly of actin regulators and their relative proportions in a cell-free system that generates filopodia-like structures (FLS). We found that heterogeneous mixtures of regulators could give rise to morphologically similar structures and that the FLS actin bundles exhibited simple dynamic behaviour of growth and shrinkage. To explain these observations, we combined experiment with theory, and found that stochastic fluctuations between redundant actin regulatory subcomplexes can account for the actin dynamics. Comparing the localizations of a variety of endogenous actin regulators in Drosophila embryos and distributions of filopodia lengths yielded similar conclusions of heterogenous actin regulatory complexes and filopodia lengths governed by a stochastic growth process. Our results explain how weakly-associating assemblies of regulatory proteins can produce robust functional outcomes.

cell biology