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Vol. 18, Issue 11, 4377-4386, November 2007

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Rab27b Is Expressed in a Wide Range of Exocytic Cells and Involved in the Delivery of Secretory Granules Near the Plasma Membrane

Hiroshi Gomi^*, Kenichi Mori^*, Shigeyoshi Itohara, and Tetsuro Izumi^*

*Laboratory of Molecular Endocrinology and Metabolism, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512, Japan; and Laboratory for Behavioral Genetics, Brain Science Institute, Institute of Physical and Chemical Research, Wako 351-0198, Japan

Submitted May 4, 2007; Revised June 29, 2007; Accepted August 17, 2007
Monitoring Editor: Francis Barr

Rab proteins regulate multiple, complex processes of membrane traffic. Among these proteins, Rab27a has been shown to function specifically in regulated exocytic pathways. However, the roles of Rab27b, another Rab27 subfamily member, have not been well characterized. We disrupted the Rab27b gene in mice. The targeting vector was designed to insert LacZ downstream of the initiation codon of the Rab27b gene so that the authentic promoter should drive this reporter gene. A comprehensive analysis of Rab27b expression using this mouse strain indicated that it is widely expressed not only in canonical secretory cells, but also in neurons and cells involved in surface protection and mechanical extension. To evaluate the function in pituitary endocrine cells where the isoform Rab27a is coexpressed, we generated Rab27a/Rab27b double knockout mice by crossing Rab27b knockout mice with Rab27a-mutated ashen mice. The polarized distribution of secretory granules close to the plasma membrane was markedly impaired in the pituitary of double knockout mice, indicating that the Rab27 subfamily is involved in the delivery of granules near the exocytic site. In conjunction with a phenotype having a pituitary devoid of the Rab27 effector granuphilin, we discuss the relationship between the residence and the releasable pool of granules.

Address correspondence to: Tetsuro Izumi (tizumi{at}showa.gunma-u.ac.jp).

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