Connexins in Lens Development and Cataractogenesis
Xiaohua Gong Æ Catherine Cheng Æ Chun-hong Xia
Received: 27 April 2007 / Accepted: 4 May 2007 / Published online: 20 June 2007
Ó
Springer Science+Business Media, LLC 2007
Abstract The lens is an avascular organ that transmits
and focuses light images onto the retina. Intercellular gap
junction channels, formed by at least three different
connexin protein subunits, a1 (connexin43 or Gja1), a3
(connexin46 or Gja3) and a8 (connexin50 or Gja8), are
utilized to transport metabolites, ions and water in the lens.
In combination with physiological and biochemical anal-
yses, recent genetic studies have significantly improved our
understanding about the roles of diverse gap junction
channels formed by a3 and a8 connexin subunits during
lens development and cataract formation. These studies
have demonstrated that a3 connexin is essential for lens
transparency while a8 connexin is important for lens
growth and transparency. Diverse gap junction channels
formed by a3 and a8 subunits are important for the dif-
ferentiation, elongation and maturation of lens fiber cells.
Aberrant gap junction communication, caused by altera-
tions of channel assembly, channel gating or channel
conductance, can lead to different types of cataracts. These
findings provide some molecular insights for essential roles
of connexins and gap junctions in lens formation and the
establishment and maintenance of lifelong lens transpar-
ency.
Keywords Connexin Á Lens Á Cataractogenesis
Introduction
Intercellular gap junction channels provide pathways for
metabolic and electrical coupling between cells in excit-
atory and nonexcitatory tissues. Gap junction channels
consist of connexin protein subunits. Most of cells utilize
more than one type of connexin subunits to form gap
junction channels, and different cells also express various
types of connexin subunits from a gene family that has
more than 20 members. One of the main subjects in the gap
junction research is to understand why and how different
connexin isoforms are utilized in cells for the physiological
needs of a given organ. The eye lens is one of the simplest
developmental models to understand cell proliferation,
differentiation and maturation in vivo. The transparent lens
is also a unique aging model for investigating cell physi-
ology and protein chemistry. Multiple isoforms of the
connexin gene family are expressed in the lens. In addition,
mouse lens and human lens share many similar features in
anatomy, physiology, biochemistry, development and dis-
ease (such as cataract). Therefore, we select the mouse lens
as our model system and investigate the function of gap
junction channels by using a modern genetic approach in
combination with techniques of molecular and cellular
biology, electrophysiology and biochemistry.
Functional Differences between a3 and a8 Connexins in
Lens Development
A mature lens is composed of elongated lens fiber cells
covered with a monolayer of epithelial cells on the anterior
hemisphere. The lens is formed through several sequential
events: (1) the lens vesicle forms at an early embryonic
stage, (2) posterior lens vesicle cells elongate to become
X. Gong Á C.-h. Xia
School of Optometry and Vision Science Program, University of
California, Berkeley, Berkeley, CA 94720, USA
X. Gong (&) Á C. Cheng
UC Berkeley/UCSF Joint Graduate Program in Bioengineering,
University of California, Berkeley, Berkeley, CA 94720, USA
e-mail: xgong@berkeley.edu
123
J Membrane Biol (2007) 218:9–12
DOI 10.1007/s00232-007-9033-0
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