Mechanisms Underlying the Initiation and Dynamics of Neuronal Filopodia: From Neurite Formation to Synaptogenesis - International Review of Cell and Molecular Biology - page 144

The role of KIF2A in the regulation of collateral length is to negatively
regulate microtubule polymerization through its depolymerizing activity.
KIF2A may thus work in concert with other molecular systems in filopo-
dia (e.g. drebrin and septin 7) to promote the maintenance and continued
polymerization of microtubules in axonal filopodia, thereby promoting
branch elongation. Finally, the actin and microtubule-binding protein,
MAP1B, negatively regulates the number of axonal filopodia and branches
( Bouquet et al., 2004 ), albeit through unknown mechanisms.
6. CONCLUDING REMARKS
The study of filopodia in highly polarized neurons has provided mul-
tiple insights into the complexity of an otherwise rather simple structure
in appearance, the filopodium. Some of the aspects of neuronal filopodia
may be restricted to neurons due to this cell type's complicated biology.
However, the insights gained by the study of neuronal filopodia may be
considered jump off points for the continued analysis of nonneuronal
filopodia beyond the canonical signaling and cytoskeletal perspectives.
Aspects of neuronal structures derived from filopodia may hold cues for
the understanding of analogous nonneuronal structures. For example, the
invadopodia of breast cancer cells exhibit many similarities to axon collat-
eral branches spanning both the signaling mechanisms (e.g. PI3K) and the
role of microtubules and actin cytoskeleton regulatory proteins ( Murphy
and Courtneidge, 2011 ; Yamaguchi et al., 2011 ). The study of neurons has
also emphasized the role of localized protein synthesis in the regulation of
cell morphology and physiology, and lessons learned from neurons may
well apply to other cells and disease states ( Shestakova et al., 1999 ). As
we seek an understanding of the generalities underlying cellular function,
the study of some of the most peculiar and specialized cells in nature is
likely to reveal unappreciated, but general, complexities ( DeRosier and
Tilney, 2000 ).
ACKNOWLEDGMENTS
The writing of this review was supported in part by NIH grant NS048090. I wish to
acknowledge and thank the collaborators who have contributed to my laboratory's efforts
at elucidating the mechanisms of neuronal filopodia and branch formation (Dr J. Chilton,
Dr P. Gordon-Weeks, Dr K. Greif, Dr L. Lanier, Dr E. Spiliotis, Dr T. Svitkina and Dr J.
Twiss).