Cell Biology

Caught Off Balance

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Science  09 Jul 2010:
Vol. 329, Issue 5988, pp. 121
DOI: 10.1126/science.329.5988.121-a

Otoconia: normal, abnormal (lower center), absent (lower right).

CREDIT: MARIÑO ET AL., J. CLIN. INVEST. 120, 10.1172/JCI42601 (2010)

An episode of dizziness, no matter how brief, reminds us that our body performs important physiological functions that we take for granted. Our sense of balance is dependent on small crystals in the inner ear called otoconia. These crystals are embedded within a fibrous extracellular matrix that couples the force of gravity to the cilia of sensory cells, which in turn send signals to the nervous system. The biosynthesis of otoconia occurs during fetal development when core proteins secreted by vestibular epithelial cells form a proteinaceous matrix that sequesters calcium carbonate. Little is known about the genes and cellular processes involved in otoconial assembly and maintenance.

Mariño et al. have discovered that a degradative cellular process called autophagy is essential for otoconial biogenesis. Mice genetically deficient in a protein that plays a key role in autophagy, Atg4b, showed behaviors consistent with inner ear defects, such as head tilting, circling movements, and disorientation in swimming tests. These behaviors were accompanied by the absence of otoconia or by the presence of morphologically abnormal otoconia. Similar abnormalities were seen in mice deficient in Atg5, which like Atg4 appears to be important in the secretion and assembly of otoconial core proteins. Further mechanistic investigation of how these small but critical crystals are made and maintained throughout life may yield new treatments for balance-related disorders, which are common in the elderly and can also be a side effect of certain antibiotics.

J. Clin. Invest. 120, 10.1172/JCI42601 (2010).

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